/ en /news/why-brain-cancer-often-resistant-immunotherapy <span class="field field--name-title field--type-string field--label-hidden"><h1>Why brain cancer is often resistant to immunotherapy</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-02-26T11:00:00-05:00" class="datetime">February 26, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Why brain cancer is often resistant to immunotherapy</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers find four coordinated gene expression programs in immune cells from glioma tumors, including two that could lead to immunotherapy resistance.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-02-26T11:00:00-05:00" title="Wednesday, February 26, 2025 - 11:00" class="datetime">February 26, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/news/images/2022/DMG.jpeg?itok=fzytTJnT 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/news/images/2022/DMG.jpeg?itok=fzytTJnT 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/news/images/2022/DMG.jpeg?itok=X4LKDbZu 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/news/images/2022/DMG.jpeg?itok=GnO45Je- 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/news/images/2022/DMG.jpeg?itok=52daQv6W 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/news/images/2022/DMG.jpeg?itok=lEP_noFu 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/news/images/2022/DMG.jpeg?itok=lEP_noFu" alt="MRI of a diffuse midline glioma" title="MRI of a diffuse midline glioma" typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Case courtesy of Dr. Jeremy Jones, radiopaedia.org. From the case rID: 68487 </div> <div class="media-caption__description"> MRI of a diffuse midline glioma </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/623/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use 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href="/news/researchers-identify-source-brain-cancers-deadly-transformation"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=UGgbAdBO 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=UGgbAdBO 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=7HxK5LZ1 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=7HxK5LZ1 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=8bYlfLPg 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=lU9aN5g2 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=lU9aN5g2" alt="Microscopy image shows glioma tumor cells in blue and pink." title="Microscopy image shows glioma tumor cells in blue and pink." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-source-brain-cancers-deadly-transformation" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify source of a brain cancer’s deadly transformation</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Immunotherapy has revolutionized the treatment of many cancers, but brain tumors such as gliomas remain particularly difficult to treat, in part because they potently suppress immune responses.</p> <p>New findings from researchers at the ӳ����ý of MIT and Harvard and the Dana-Farber Cancer Institute (DFCI) could help make immunotherapies for brain cancer more effective.</p> <p>The team analyzed almost 200,000 individual immune cells called myeloid cells from tumor samples from patients with glioma, the most common and aggressive type of primary brain cancer. In a new study in <em><a href="https://www.nature.com/articles/s41586-025-08633-8" target="_blank">Nature</a></em>, the researchers found four gene expression “programs” — sets of genes with coordinated activity — that either suppress the immune system or make it more active. They also found that patients treated with dexamethasone, a common treatment for brain cancer patients, showed signs of one of the immunosuppressive programs, suggesting that this drug could reduce the effectiveness of immunotherapy.</p> <p>The team says that defining and understanding what drives these programs could one day help researchers target them with new drugs to dial up or down specific parts of the immune system to improve patient response to immunotherapy.</p> <p>“This study provides us with the data we need to create myeloid-targeting strategies to modulate these programs and make immunotherapies more effective for brain tumor patients,” said Tyler Miller, co-first author on the study and a resident in clinical pathology at Massachusetts General Hospital when the study began.</p> <p><a href="/node/4552">Bradley Bernstein</a>, an institute member at the ӳ����ý and chair of the cancer biology department at DFCI, was the study’s senior author.</p> <p>“These gene signatures provide a roadmap that the field can use to study myeloid cells and how they impact the way brain tumors respond to therapy,” Bernstein said.</p> <p>Chadi El Farran, a postdoctoral researcher in Bernstein’s lab, and Charles Couturier, a postdoctoral researcher in <a href="/node/446101">Alex Shalek’s lab</a> at the ӳ����ý and MIT, were co-first authors on the work with Miller.</p> <h2>Clustering cells</h2> <p>As a pathology resident, Miller watched treatment after treatment fail in patients with gliomas. He’d seen the difference immunotherapy made for other cancers, and wanted to know how to improve them for brain cancer.</p> <p>At the ӳ����ý, he decided to focus on myeloid cells, which make up to half of the cells in many brain tumors and can suppress the immune system, preventing immunotherapies from working well. Using single-cell RNA sequencing, which probes gene expression in individual cells, Miller and his colleagues examined nearly 200,000 cells from 85 different glioma tumors.</p> <p>To do this, the team used a different approach to single-cell analysis. Scientists typically analyze single-cell data by grouping similar cells together by gene expression related to cell type. But this approach can cause researchers to overlook features such as gene expression patterns related to a cell’s activities, which are important in myeloid cells.&nbsp;</p> <p>So the researchers used a method developed at the ӳ����ý in 2019 called <a href="https://elifesciences.org/articles/43803" target="_blank">consensus non-negative matrix factorization (cNMF)</a>, which can define cells by their identity and activity independently. With this approach, the team identified four programs shaping the immune system. In two, the immune system was inflammatory; it was activated and potentially trying to attack the tumor. The other two programs, found in advanced tumors, were immunosuppressive, partially shutting down the immune system and hampering its ability to fight cancer.</p> <h2>Treatment insights</h2> <p>One of the immunosuppressive programs appeared in patients who had been treated with dexamethasone, a steroid often used to reduce swelling in the brain when a patient first develops symptoms and before they receive immunotherapy. Though scientists knew that dexamethasone is immunosuppressive, they’d previously thought this was primarily due to the medication’s effects on T cells. But the new findings suggest that the drug also strongly impacts myeloid cells, and that dexamethasone should be prescribed more sparingly to improve the efficacy of immunotherapies.</p> <p>“We hope this will spur additional studies to identify ways to tackle edema [brain swelling] using different drugs and also to think about how we design clinical trials based on those results,” Miller said.</p> <p>He and his colleagues also created organoids, or three-dimensional assemblies of cells in the lab, from pieces of patient tumors, and treated the cultures with dexamethasone. They found that myeloid cells in the organoids continued to express the immunosuppressive programs long after they’d removed the drug, suggesting that the steroid could affect immunotherapy response even if only given to patients for a short time.&nbsp;</p> <p>Using the organoids, the researchers also found that cell signaling molecules such as the inflammatory protein IL-1β and the growth factor TGF-β pushed the tumors to express the other immunosuppressive cell program.&nbsp;</p> <p>Miller says scientists could one day manipulate the four programs with drugs to make immunotherapies more effective. In the meantime, he hopes that their approach highlights the importance of considering myeloid cells and will inspire other groups to study their roles in other tumors and patient populations.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the Brain Tumour Charity, the American Brain Tumor Association, The Brilliant Night Foundation, the National Institutes of Health, the Ludwig Center at Harvard, and the Emerson Collective.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Miller TE, El Farran CA, Couturier CP et al. <a href="https://www.nature.com/articles/s41586-025-08633-8" target="_blank">Programs, origins and immunomodulatory functions of myeloid cells in glioma</a>. <em>Nature</em>. Online February 26, 2025. DOI: 10.1038/s41586-025-08633-8.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/single-cell" hreflang="en">Single Cell</a></div> <div class="field__item"><a href="/broad-tags/brad-bernstein" hreflang="en">Brad Bernstein</a></div> </div> </div> </div> </div> </div> Wed, 26 Feb 2025 16:00:00 +0000 adicorat 5558236 at /news/study-finds-surprising-way-genetic-mutation-causes-huntingtons-disease-transforming <span class="field field--name-title field--type-string field--label-hidden"><h1>Why brain cancer is often resistant to immunotherapy</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-02-26T11:00:00-05:00" class="datetime">February 26, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Why brain cancer is often resistant to immunotherapy</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers find four coordinated gene expression programs in immune cells from glioma tumors, including two that could lead to immunotherapy resistance.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-02-26T11:00:00-05:00" title="Wednesday, February 26, 2025 - 11:00" class="datetime">February 26, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/news/images/2022/DMG.jpeg?itok=fzytTJnT 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/news/images/2022/DMG.jpeg?itok=fzytTJnT 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/news/images/2022/DMG.jpeg?itok=X4LKDbZu 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/news/images/2022/DMG.jpeg?itok=GnO45Je- 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/news/images/2022/DMG.jpeg?itok=52daQv6W 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/news/images/2022/DMG.jpeg?itok=lEP_noFu 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/news/images/2022/DMG.jpeg?itok=lEP_noFu" alt="MRI of a diffuse midline glioma" title="MRI of a diffuse midline glioma" typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Case courtesy of Dr. Jeremy Jones, radiopaedia.org. From the case rID: 68487 </div> <div class="media-caption__description"> MRI of a diffuse midline glioma </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/623/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use 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block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/single-cell-study-childhood-brain-tumor-affirms-importance-context" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/single-cell-study-childhood-brain-tumor-affirms-importance-context"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=eNugrUoW 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=eNugrUoW 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=hv_xiYhy 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=hv_xiYhy 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=HE-WuXIF 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=nlW3AR-k 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=nlW3AR-k" alt="Lauren Solomon, ӳ����ý Communications" typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/single-cell-study-childhood-brain-tumor-affirms-importance-context" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Single-cell study in a childhood brain tumor affirms the importance of context</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/researchers-identify-source-brain-cancers-deadly-transformation" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-identify-source-brain-cancers-deadly-transformation"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=UGgbAdBO 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=UGgbAdBO 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=7HxK5LZ1 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=7HxK5LZ1 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=8bYlfLPg 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=lU9aN5g2 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=lU9aN5g2" alt="Microscopy image shows glioma tumor cells in blue and pink." title="Microscopy image shows glioma tumor cells in blue and pink." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-source-brain-cancers-deadly-transformation" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify source of a brain cancer’s deadly transformation</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Immunotherapy has revolutionized the treatment of many cancers, but brain tumors such as gliomas remain particularly difficult to treat, in part because they potently suppress immune responses.</p> <p>New findings from researchers at the ӳ����ý of MIT and Harvard and the Dana-Farber Cancer Institute (DFCI) could help make immunotherapies for brain cancer more effective.</p> <p>The team analyzed almost 200,000 individual immune cells called myeloid cells from tumor samples from patients with glioma, the most common and aggressive type of primary brain cancer. In a new study in <em><a href="https://www.nature.com/articles/s41586-025-08633-8" target="_blank">Nature</a></em>, the researchers found four gene expression “programs” — sets of genes with coordinated activity — that either suppress the immune system or make it more active. They also found that patients treated with dexamethasone, a common treatment for brain cancer patients, showed signs of one of the immunosuppressive programs, suggesting that this drug could reduce the effectiveness of immunotherapy.</p> <p>The team says that defining and understanding what drives these programs could one day help researchers target them with new drugs to dial up or down specific parts of the immune system to improve patient response to immunotherapy.</p> <p>“This study provides us with the data we need to create myeloid-targeting strategies to modulate these programs and make immunotherapies more effective for brain tumor patients,” said Tyler Miller, co-first author on the study and a resident in clinical pathology at Massachusetts General Hospital when the study began.</p> <p><a href="/node/4552">Bradley Bernstein</a>, an institute member at the ӳ����ý and chair of the cancer biology department at DFCI, was the study’s senior author.</p> <p>“These gene signatures provide a roadmap that the field can use to study myeloid cells and how they impact the way brain tumors respond to therapy,” Bernstein said.</p> <p>Chadi El Farran, a postdoctoral researcher in Bernstein’s lab, and Charles Couturier, a postdoctoral researcher in <a href="/node/446101">Alex Shalek’s lab</a> at the ӳ����ý and MIT, were co-first authors on the work with Miller.</p> <h2>Clustering cells</h2> <p>As a pathology resident, Miller watched treatment after treatment fail in patients with gliomas. He’d seen the difference immunotherapy made for other cancers, and wanted to know how to improve them for brain cancer.</p> <p>At the ӳ����ý, he decided to focus on myeloid cells, which make up to half of the cells in many brain tumors and can suppress the immune system, preventing immunotherapies from working well. Using single-cell RNA sequencing, which probes gene expression in individual cells, Miller and his colleagues examined nearly 200,000 cells from 85 different glioma tumors.</p> <p>To do this, the team used a different approach to single-cell analysis. Scientists typically analyze single-cell data by grouping similar cells together by gene expression related to cell type. But this approach can cause researchers to overlook features such as gene expression patterns related to a cell’s activities, which are important in myeloid cells.&nbsp;</p> <p>So the researchers used a method developed at the ӳ����ý in 2019 called <a href="https://elifesciences.org/articles/43803" target="_blank">consensus non-negative matrix factorization (cNMF)</a>, which can define cells by their identity and activity independently. With this approach, the team identified four programs shaping the immune system. In two, the immune system was inflammatory; it was activated and potentially trying to attack the tumor. The other two programs, found in advanced tumors, were immunosuppressive, partially shutting down the immune system and hampering its ability to fight cancer.</p> <h2>Treatment insights</h2> <p>One of the immunosuppressive programs appeared in patients who had been treated with dexamethasone, a steroid often used to reduce swelling in the brain when a patient first develops symptoms and before they receive immunotherapy. Though scientists knew that dexamethasone is immunosuppressive, they’d previously thought this was primarily due to the medication’s effects on T cells. But the new findings suggest that the drug also strongly impacts myeloid cells, and that dexamethasone should be prescribed more sparingly to improve the efficacy of immunotherapies.</p> <p>“We hope this will spur additional studies to identify ways to tackle edema [brain swelling] using different drugs and also to think about how we design clinical trials based on those results,” Miller said.</p> <p>He and his colleagues also created organoids, or three-dimensional assemblies of cells in the lab, from pieces of patient tumors, and treated the cultures with dexamethasone. They found that myeloid cells in the organoids continued to express the immunosuppressive programs long after they’d removed the drug, suggesting that the steroid could affect immunotherapy response even if only given to patients for a short time.&nbsp;</p> <p>Using the organoids, the researchers also found that cell signaling molecules such as the inflammatory protein IL-1β and the growth factor TGF-β pushed the tumors to express the other immunosuppressive cell program.&nbsp;</p> <p>Miller says scientists could one day manipulate the four programs with drugs to make immunotherapies more effective. In the meantime, he hopes that their approach highlights the importance of considering myeloid cells and will inspire other groups to study their roles in other tumors and patient populations.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the Brain Tumour Charity, the American Brain Tumor Association, The Brilliant Night Foundation, the National Institutes of Health, the Ludwig Center at Harvard, and the Emerson Collective.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Miller TE, El Farran CA, Couturier CP et al. <a href="https://www.nature.com/articles/s41586-025-08633-8" target="_blank">Programs, origins and immunomodulatory functions of myeloid cells in glioma</a>. <em>Nature</em>. Online February 26, 2025. DOI: 10.1038/s41586-025-08633-8.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/single-cell" hreflang="en">Single Cell</a></div> <div class="field__item"><a href="/broad-tags/brad-bernstein" hreflang="en">Brad Bernstein</a></div> </div> </div> </div> </div> </div> Thu, 16 Jan 2025 16:00:00 +0000 adicorat 5558011 at /news/researchers-map-communities-single-cells-metastatic-breast-cancers <span class="field field--name-title field--type-string field--label-hidden"><h1>Why brain cancer is often resistant to immunotherapy</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-02-26T11:00:00-05:00" class="datetime">February 26, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Why brain cancer is often resistant to immunotherapy</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers find four coordinated gene expression programs in immune cells from glioma tumors, including two that could lead to immunotherapy resistance.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-02-26T11:00:00-05:00" title="Wednesday, February 26, 2025 - 11:00" class="datetime">February 26, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/news/images/2022/DMG.jpeg?itok=fzytTJnT 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/news/images/2022/DMG.jpeg?itok=fzytTJnT 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/news/images/2022/DMG.jpeg?itok=X4LKDbZu 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/news/images/2022/DMG.jpeg?itok=GnO45Je- 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/news/images/2022/DMG.jpeg?itok=52daQv6W 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/news/images/2022/DMG.jpeg?itok=lEP_noFu 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/news/images/2022/DMG.jpeg?itok=lEP_noFu" alt="MRI of a diffuse midline glioma" title="MRI of a diffuse midline glioma" typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Case courtesy of Dr. Jeremy Jones, radiopaedia.org. From the case rID: 68487 </div> <div class="media-caption__description"> MRI of a diffuse midline glioma </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/623/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use 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field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/single-cell-study-childhood-brain-tumor-affirms-importance-context"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=eNugrUoW 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=eNugrUoW 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=hv_xiYhy 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=hv_xiYhy 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=HE-WuXIF 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=nlW3AR-k 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=nlW3AR-k" alt="Lauren Solomon, ӳ����ý Communications" typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/single-cell-study-childhood-brain-tumor-affirms-importance-context" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Single-cell study in a childhood brain tumor affirms the importance of context</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/researchers-identify-source-brain-cancers-deadly-transformation" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-identify-source-brain-cancers-deadly-transformation"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=UGgbAdBO 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=UGgbAdBO 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=7HxK5LZ1 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=7HxK5LZ1 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=8bYlfLPg 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=lU9aN5g2 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=lU9aN5g2" alt="Microscopy image shows glioma tumor cells in blue and pink." title="Microscopy image shows glioma tumor cells in blue and pink." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-source-brain-cancers-deadly-transformation" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify source of a brain cancer’s deadly transformation</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Immunotherapy has revolutionized the treatment of many cancers, but brain tumors such as gliomas remain particularly difficult to treat, in part because they potently suppress immune responses.</p> <p>New findings from researchers at the ӳ����ý of MIT and Harvard and the Dana-Farber Cancer Institute (DFCI) could help make immunotherapies for brain cancer more effective.</p> <p>The team analyzed almost 200,000 individual immune cells called myeloid cells from tumor samples from patients with glioma, the most common and aggressive type of primary brain cancer. In a new study in <em><a href="https://www.nature.com/articles/s41586-025-08633-8" target="_blank">Nature</a></em>, the researchers found four gene expression “programs” — sets of genes with coordinated activity — that either suppress the immune system or make it more active. They also found that patients treated with dexamethasone, a common treatment for brain cancer patients, showed signs of one of the immunosuppressive programs, suggesting that this drug could reduce the effectiveness of immunotherapy.</p> <p>The team says that defining and understanding what drives these programs could one day help researchers target them with new drugs to dial up or down specific parts of the immune system to improve patient response to immunotherapy.</p> <p>“This study provides us with the data we need to create myeloid-targeting strategies to modulate these programs and make immunotherapies more effective for brain tumor patients,” said Tyler Miller, co-first author on the study and a resident in clinical pathology at Massachusetts General Hospital when the study began.</p> <p><a href="/node/4552">Bradley Bernstein</a>, an institute member at the ӳ����ý and chair of the cancer biology department at DFCI, was the study’s senior author.</p> <p>“These gene signatures provide a roadmap that the field can use to study myeloid cells and how they impact the way brain tumors respond to therapy,” Bernstein said.</p> <p>Chadi El Farran, a postdoctoral researcher in Bernstein’s lab, and Charles Couturier, a postdoctoral researcher in <a href="/node/446101">Alex Shalek’s lab</a> at the ӳ����ý and MIT, were co-first authors on the work with Miller.</p> <h2>Clustering cells</h2> <p>As a pathology resident, Miller watched treatment after treatment fail in patients with gliomas. He’d seen the difference immunotherapy made for other cancers, and wanted to know how to improve them for brain cancer.</p> <p>At the ӳ����ý, he decided to focus on myeloid cells, which make up to half of the cells in many brain tumors and can suppress the immune system, preventing immunotherapies from working well. Using single-cell RNA sequencing, which probes gene expression in individual cells, Miller and his colleagues examined nearly 200,000 cells from 85 different glioma tumors.</p> <p>To do this, the team used a different approach to single-cell analysis. Scientists typically analyze single-cell data by grouping similar cells together by gene expression related to cell type. But this approach can cause researchers to overlook features such as gene expression patterns related to a cell’s activities, which are important in myeloid cells.&nbsp;</p> <p>So the researchers used a method developed at the ӳ����ý in 2019 called <a href="https://elifesciences.org/articles/43803" target="_blank">consensus non-negative matrix factorization (cNMF)</a>, which can define cells by their identity and activity independently. With this approach, the team identified four programs shaping the immune system. In two, the immune system was inflammatory; it was activated and potentially trying to attack the tumor. The other two programs, found in advanced tumors, were immunosuppressive, partially shutting down the immune system and hampering its ability to fight cancer.</p> <h2>Treatment insights</h2> <p>One of the immunosuppressive programs appeared in patients who had been treated with dexamethasone, a steroid often used to reduce swelling in the brain when a patient first develops symptoms and before they receive immunotherapy. Though scientists knew that dexamethasone is immunosuppressive, they’d previously thought this was primarily due to the medication’s effects on T cells. But the new findings suggest that the drug also strongly impacts myeloid cells, and that dexamethasone should be prescribed more sparingly to improve the efficacy of immunotherapies.</p> <p>“We hope this will spur additional studies to identify ways to tackle edema [brain swelling] using different drugs and also to think about how we design clinical trials based on those results,” Miller said.</p> <p>He and his colleagues also created organoids, or three-dimensional assemblies of cells in the lab, from pieces of patient tumors, and treated the cultures with dexamethasone. They found that myeloid cells in the organoids continued to express the immunosuppressive programs long after they’d removed the drug, suggesting that the steroid could affect immunotherapy response even if only given to patients for a short time.&nbsp;</p> <p>Using the organoids, the researchers also found that cell signaling molecules such as the inflammatory protein IL-1β and the growth factor TGF-β pushed the tumors to express the other immunosuppressive cell program.&nbsp;</p> <p>Miller says scientists could one day manipulate the four programs with drugs to make immunotherapies more effective. In the meantime, he hopes that their approach highlights the importance of considering myeloid cells and will inspire other groups to study their roles in other tumors and patient populations.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the Brain Tumour Charity, the American Brain Tumor Association, The Brilliant Night Foundation, the National Institutes of Health, the Ludwig Center at Harvard, and the Emerson Collective.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Miller TE, El Farran CA, Couturier CP et al. <a href="https://www.nature.com/articles/s41586-025-08633-8" target="_blank">Programs, origins and immunomodulatory functions of myeloid cells in glioma</a>. <em>Nature</em>. Online February 26, 2025. DOI: 10.1038/s41586-025-08633-8.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/single-cell" hreflang="en">Single Cell</a></div> <div class="field__item"><a href="/broad-tags/brad-bernstein" hreflang="en">Brad Bernstein</a></div> </div> </div> </div> </div> </div> Wed, 30 Oct 2024 15:02:43 +0000 Corie Lok 5557661 at /news/new-machine-learning-based-single-cell-search-engine-makes-cell-annotation-faster-more <span class="field field--name-title field--type-string field--label-hidden"><h1>Why brain cancer is often resistant to immunotherapy</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-02-26T11:00:00-05:00" class="datetime">February 26, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Why brain cancer is often resistant to immunotherapy</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers find four coordinated gene expression programs in immune cells from glioma tumors, including two that could lead to immunotherapy resistance.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-02-26T11:00:00-05:00" title="Wednesday, February 26, 2025 - 11:00" class="datetime">February 26, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/news/images/2022/DMG.jpeg?itok=fzytTJnT 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/news/images/2022/DMG.jpeg?itok=fzytTJnT 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/news/images/2022/DMG.jpeg?itok=X4LKDbZu 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/news/images/2022/DMG.jpeg?itok=GnO45Je- 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/news/images/2022/DMG.jpeg?itok=52daQv6W 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/news/images/2022/DMG.jpeg?itok=lEP_noFu 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/news/images/2022/DMG.jpeg?itok=lEP_noFu" alt="MRI of a diffuse midline glioma" title="MRI of a diffuse midline glioma" typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Case courtesy of Dr. Jeremy Jones, radiopaedia.org. From the case rID: 68487 </div> <div class="media-caption__description"> MRI of a diffuse midline glioma </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/623/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use 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block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/single-cell-study-childhood-brain-tumor-affirms-importance-context" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/single-cell-study-childhood-brain-tumor-affirms-importance-context"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=eNugrUoW 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=eNugrUoW 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=hv_xiYhy 1x" 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href="/news/researchers-identify-source-brain-cancers-deadly-transformation"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=UGgbAdBO 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=UGgbAdBO 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=7HxK5LZ1 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=7HxK5LZ1 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=8bYlfLPg 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=lU9aN5g2 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=lU9aN5g2" alt="Microscopy image shows glioma tumor cells in blue and pink." title="Microscopy image shows glioma tumor cells in blue and pink." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-source-brain-cancers-deadly-transformation" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify source of a brain cancer’s deadly transformation</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Immunotherapy has revolutionized the treatment of many cancers, but brain tumors such as gliomas remain particularly difficult to treat, in part because they potently suppress immune responses.</p> <p>New findings from researchers at the ӳ����ý of MIT and Harvard and the Dana-Farber Cancer Institute (DFCI) could help make immunotherapies for brain cancer more effective.</p> <p>The team analyzed almost 200,000 individual immune cells called myeloid cells from tumor samples from patients with glioma, the most common and aggressive type of primary brain cancer. In a new study in <em><a href="https://www.nature.com/articles/s41586-025-08633-8" target="_blank">Nature</a></em>, the researchers found four gene expression “programs” — sets of genes with coordinated activity — that either suppress the immune system or make it more active. They also found that patients treated with dexamethasone, a common treatment for brain cancer patients, showed signs of one of the immunosuppressive programs, suggesting that this drug could reduce the effectiveness of immunotherapy.</p> <p>The team says that defining and understanding what drives these programs could one day help researchers target them with new drugs to dial up or down specific parts of the immune system to improve patient response to immunotherapy.</p> <p>“This study provides us with the data we need to create myeloid-targeting strategies to modulate these programs and make immunotherapies more effective for brain tumor patients,” said Tyler Miller, co-first author on the study and a resident in clinical pathology at Massachusetts General Hospital when the study began.</p> <p><a href="/node/4552">Bradley Bernstein</a>, an institute member at the ӳ����ý and chair of the cancer biology department at DFCI, was the study’s senior author.</p> <p>“These gene signatures provide a roadmap that the field can use to study myeloid cells and how they impact the way brain tumors respond to therapy,” Bernstein said.</p> <p>Chadi El Farran, a postdoctoral researcher in Bernstein’s lab, and Charles Couturier, a postdoctoral researcher in <a href="/node/446101">Alex Shalek’s lab</a> at the ӳ����ý and MIT, were co-first authors on the work with Miller.</p> <h2>Clustering cells</h2> <p>As a pathology resident, Miller watched treatment after treatment fail in patients with gliomas. He’d seen the difference immunotherapy made for other cancers, and wanted to know how to improve them for brain cancer.</p> <p>At the ӳ����ý, he decided to focus on myeloid cells, which make up to half of the cells in many brain tumors and can suppress the immune system, preventing immunotherapies from working well. Using single-cell RNA sequencing, which probes gene expression in individual cells, Miller and his colleagues examined nearly 200,000 cells from 85 different glioma tumors.</p> <p>To do this, the team used a different approach to single-cell analysis. Scientists typically analyze single-cell data by grouping similar cells together by gene expression related to cell type. But this approach can cause researchers to overlook features such as gene expression patterns related to a cell’s activities, which are important in myeloid cells.&nbsp;</p> <p>So the researchers used a method developed at the ӳ����ý in 2019 called <a href="https://elifesciences.org/articles/43803" target="_blank">consensus non-negative matrix factorization (cNMF)</a>, which can define cells by their identity and activity independently. With this approach, the team identified four programs shaping the immune system. In two, the immune system was inflammatory; it was activated and potentially trying to attack the tumor. The other two programs, found in advanced tumors, were immunosuppressive, partially shutting down the immune system and hampering its ability to fight cancer.</p> <h2>Treatment insights</h2> <p>One of the immunosuppressive programs appeared in patients who had been treated with dexamethasone, a steroid often used to reduce swelling in the brain when a patient first develops symptoms and before they receive immunotherapy. Though scientists knew that dexamethasone is immunosuppressive, they’d previously thought this was primarily due to the medication’s effects on T cells. But the new findings suggest that the drug also strongly impacts myeloid cells, and that dexamethasone should be prescribed more sparingly to improve the efficacy of immunotherapies.</p> <p>“We hope this will spur additional studies to identify ways to tackle edema [brain swelling] using different drugs and also to think about how we design clinical trials based on those results,” Miller said.</p> <p>He and his colleagues also created organoids, or three-dimensional assemblies of cells in the lab, from pieces of patient tumors, and treated the cultures with dexamethasone. They found that myeloid cells in the organoids continued to express the immunosuppressive programs long after they’d removed the drug, suggesting that the steroid could affect immunotherapy response even if only given to patients for a short time.&nbsp;</p> <p>Using the organoids, the researchers also found that cell signaling molecules such as the inflammatory protein IL-1β and the growth factor TGF-β pushed the tumors to express the other immunosuppressive cell program.&nbsp;</p> <p>Miller says scientists could one day manipulate the four programs with drugs to make immunotherapies more effective. In the meantime, he hopes that their approach highlights the importance of considering myeloid cells and will inspire other groups to study their roles in other tumors and patient populations.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the Brain Tumour Charity, the American Brain Tumor Association, The Brilliant Night Foundation, the National Institutes of Health, the Ludwig Center at Harvard, and the Emerson Collective.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Miller TE, El Farran CA, Couturier CP et al. <a href="https://www.nature.com/articles/s41586-025-08633-8" target="_blank">Programs, origins and immunomodulatory functions of myeloid cells in glioma</a>. <em>Nature</em>. Online February 26, 2025. DOI: 10.1038/s41586-025-08633-8.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/single-cell" hreflang="en">Single Cell</a></div> <div class="field__item"><a href="/broad-tags/brad-bernstein" hreflang="en">Brad Bernstein</a></div> </div> </div> </div> </div> </div> Mon, 28 Oct 2024 14:55:51 +0000 Corie Lok 5557581 at /news/cellular-atlas-built-guide-precision-treatment-rheumatoid-arthritis <span class="field field--name-title field--type-string field--label-hidden"><h1>Why brain cancer is often resistant to immunotherapy</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-02-26T11:00:00-05:00" class="datetime">February 26, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Why brain cancer is often resistant to immunotherapy</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers find four coordinated gene expression programs in immune cells from glioma tumors, including two that could lead to immunotherapy resistance.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-02-26T11:00:00-05:00" title="Wednesday, February 26, 2025 - 11:00" class="datetime">February 26, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/news/images/2022/DMG.jpeg?itok=fzytTJnT 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/news/images/2022/DMG.jpeg?itok=fzytTJnT 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/news/images/2022/DMG.jpeg?itok=X4LKDbZu 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/news/images/2022/DMG.jpeg?itok=GnO45Je- 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/news/images/2022/DMG.jpeg?itok=52daQv6W 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/news/images/2022/DMG.jpeg?itok=lEP_noFu 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/news/images/2022/DMG.jpeg?itok=lEP_noFu" alt="MRI of a diffuse midline glioma" title="MRI of a diffuse midline glioma" typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Case courtesy of Dr. Jeremy Jones, radiopaedia.org. From the case rID: 68487 </div> <div class="media-caption__description"> MRI of a diffuse midline glioma </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/623/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use 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block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/single-cell-study-childhood-brain-tumor-affirms-importance-context" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/single-cell-study-childhood-brain-tumor-affirms-importance-context"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=eNugrUoW 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=eNugrUoW 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=hv_xiYhy 1x" 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in blue and pink." title="Microscopy image shows glioma tumor cells in blue and pink." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-source-brain-cancers-deadly-transformation" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify source of a brain cancer’s deadly transformation</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Immunotherapy has revolutionized the treatment of many cancers, but brain tumors such as gliomas remain particularly difficult to treat, in part because they potently suppress immune responses.</p> <p>New findings from researchers at the ӳ����ý of MIT and Harvard and the Dana-Farber Cancer Institute (DFCI) could help make immunotherapies for brain cancer more effective.</p> <p>The team analyzed almost 200,000 individual immune cells called myeloid cells from tumor samples from patients with glioma, the most common and aggressive type of primary brain cancer. In a new study in <em><a href="https://www.nature.com/articles/s41586-025-08633-8" target="_blank">Nature</a></em>, the researchers found four gene expression “programs” — sets of genes with coordinated activity — that either suppress the immune system or make it more active. They also found that patients treated with dexamethasone, a common treatment for brain cancer patients, showed signs of one of the immunosuppressive programs, suggesting that this drug could reduce the effectiveness of immunotherapy.</p> <p>The team says that defining and understanding what drives these programs could one day help researchers target them with new drugs to dial up or down specific parts of the immune system to improve patient response to immunotherapy.</p> <p>“This study provides us with the data we need to create myeloid-targeting strategies to modulate these programs and make immunotherapies more effective for brain tumor patients,” said Tyler Miller, co-first author on the study and a resident in clinical pathology at Massachusetts General Hospital when the study began.</p> <p><a href="/node/4552">Bradley Bernstein</a>, an institute member at the ӳ����ý and chair of the cancer biology department at DFCI, was the study’s senior author.</p> <p>“These gene signatures provide a roadmap that the field can use to study myeloid cells and how they impact the way brain tumors respond to therapy,” Bernstein said.</p> <p>Chadi El Farran, a postdoctoral researcher in Bernstein’s lab, and Charles Couturier, a postdoctoral researcher in <a href="/node/446101">Alex Shalek’s lab</a> at the ӳ����ý and MIT, were co-first authors on the work with Miller.</p> <h2>Clustering cells</h2> <p>As a pathology resident, Miller watched treatment after treatment fail in patients with gliomas. He’d seen the difference immunotherapy made for other cancers, and wanted to know how to improve them for brain cancer.</p> <p>At the ӳ����ý, he decided to focus on myeloid cells, which make up to half of the cells in many brain tumors and can suppress the immune system, preventing immunotherapies from working well. Using single-cell RNA sequencing, which probes gene expression in individual cells, Miller and his colleagues examined nearly 200,000 cells from 85 different glioma tumors.</p> <p>To do this, the team used a different approach to single-cell analysis. Scientists typically analyze single-cell data by grouping similar cells together by gene expression related to cell type. But this approach can cause researchers to overlook features such as gene expression patterns related to a cell’s activities, which are important in myeloid cells.&nbsp;</p> <p>So the researchers used a method developed at the ӳ����ý in 2019 called <a href="https://elifesciences.org/articles/43803" target="_blank">consensus non-negative matrix factorization (cNMF)</a>, which can define cells by their identity and activity independently. With this approach, the team identified four programs shaping the immune system. In two, the immune system was inflammatory; it was activated and potentially trying to attack the tumor. The other two programs, found in advanced tumors, were immunosuppressive, partially shutting down the immune system and hampering its ability to fight cancer.</p> <h2>Treatment insights</h2> <p>One of the immunosuppressive programs appeared in patients who had been treated with dexamethasone, a steroid often used to reduce swelling in the brain when a patient first develops symptoms and before they receive immunotherapy. Though scientists knew that dexamethasone is immunosuppressive, they’d previously thought this was primarily due to the medication’s effects on T cells. But the new findings suggest that the drug also strongly impacts myeloid cells, and that dexamethasone should be prescribed more sparingly to improve the efficacy of immunotherapies.</p> <p>“We hope this will spur additional studies to identify ways to tackle edema [brain swelling] using different drugs and also to think about how we design clinical trials based on those results,” Miller said.</p> <p>He and his colleagues also created organoids, or three-dimensional assemblies of cells in the lab, from pieces of patient tumors, and treated the cultures with dexamethasone. They found that myeloid cells in the organoids continued to express the immunosuppressive programs long after they’d removed the drug, suggesting that the steroid could affect immunotherapy response even if only given to patients for a short time.&nbsp;</p> <p>Using the organoids, the researchers also found that cell signaling molecules such as the inflammatory protein IL-1β and the growth factor TGF-β pushed the tumors to express the other immunosuppressive cell program.&nbsp;</p> <p>Miller says scientists could one day manipulate the four programs with drugs to make immunotherapies more effective. In the meantime, he hopes that their approach highlights the importance of considering myeloid cells and will inspire other groups to study their roles in other tumors and patient populations.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the Brain Tumour Charity, the American Brain Tumor Association, The Brilliant Night Foundation, the National Institutes of Health, the Ludwig Center at Harvard, and the Emerson Collective.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Miller TE, El Farran CA, Couturier CP et al. <a href="https://www.nature.com/articles/s41586-025-08633-8" target="_blank">Programs, origins and immunomodulatory functions of myeloid cells in glioma</a>. <em>Nature</em>. Online February 26, 2025. DOI: 10.1038/s41586-025-08633-8.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/single-cell" hreflang="en">Single Cell</a></div> <div class="field__item"><a href="/broad-tags/brad-bernstein" hreflang="en">Brad Bernstein</a></div> </div> </div> </div> </div> </div> Tue, 07 Nov 2023 22:33:23 +0000 tulrich@broadinstitute.org 5555981 at /news/broad-discovery-center-cambridge-opens-public-october <span class="field field--name-title field--type-string field--label-hidden"><h1>Why brain cancer is often resistant to immunotherapy</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-02-26T11:00:00-05:00" class="datetime">February 26, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Why brain cancer is often resistant to immunotherapy</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers find four coordinated gene expression programs in immune cells from glioma tumors, including two that could lead to immunotherapy resistance.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-02-26T11:00:00-05:00" title="Wednesday, February 26, 2025 - 11:00" class="datetime">February 26, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/news/images/2022/DMG.jpeg?itok=fzytTJnT 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/news/images/2022/DMG.jpeg?itok=fzytTJnT 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/news/images/2022/DMG.jpeg?itok=X4LKDbZu 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/news/images/2022/DMG.jpeg?itok=GnO45Je- 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/news/images/2022/DMG.jpeg?itok=52daQv6W 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/news/images/2022/DMG.jpeg?itok=lEP_noFu 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/news/images/2022/DMG.jpeg?itok=lEP_noFu" alt="MRI of a diffuse midline glioma" title="MRI of a diffuse midline glioma" typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Case courtesy of Dr. Jeremy Jones, radiopaedia.org. From the case rID: 68487 </div> <div class="media-caption__description"> MRI of a diffuse midline glioma </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/623/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use 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block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/single-cell-study-childhood-brain-tumor-affirms-importance-context" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/single-cell-study-childhood-brain-tumor-affirms-importance-context"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=eNugrUoW 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=eNugrUoW 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=hv_xiYhy 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=hv_xiYhy 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=HE-WuXIF 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=nlW3AR-k 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" width="220" height="186" 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href="/news/researchers-identify-source-brain-cancers-deadly-transformation"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=UGgbAdBO 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=UGgbAdBO 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=7HxK5LZ1 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=7HxK5LZ1 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=8bYlfLPg 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=lU9aN5g2 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=lU9aN5g2" alt="Microscopy image shows glioma tumor cells in blue and pink." title="Microscopy image shows glioma tumor cells in blue and pink." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-source-brain-cancers-deadly-transformation" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify source of a brain cancer’s deadly transformation</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Immunotherapy has revolutionized the treatment of many cancers, but brain tumors such as gliomas remain particularly difficult to treat, in part because they potently suppress immune responses.</p> <p>New findings from researchers at the ӳ����ý of MIT and Harvard and the Dana-Farber Cancer Institute (DFCI) could help make immunotherapies for brain cancer more effective.</p> <p>The team analyzed almost 200,000 individual immune cells called myeloid cells from tumor samples from patients with glioma, the most common and aggressive type of primary brain cancer. In a new study in <em><a href="https://www.nature.com/articles/s41586-025-08633-8" target="_blank">Nature</a></em>, the researchers found four gene expression “programs” — sets of genes with coordinated activity — that either suppress the immune system or make it more active. They also found that patients treated with dexamethasone, a common treatment for brain cancer patients, showed signs of one of the immunosuppressive programs, suggesting that this drug could reduce the effectiveness of immunotherapy.</p> <p>The team says that defining and understanding what drives these programs could one day help researchers target them with new drugs to dial up or down specific parts of the immune system to improve patient response to immunotherapy.</p> <p>“This study provides us with the data we need to create myeloid-targeting strategies to modulate these programs and make immunotherapies more effective for brain tumor patients,” said Tyler Miller, co-first author on the study and a resident in clinical pathology at Massachusetts General Hospital when the study began.</p> <p><a href="/node/4552">Bradley Bernstein</a>, an institute member at the ӳ����ý and chair of the cancer biology department at DFCI, was the study’s senior author.</p> <p>“These gene signatures provide a roadmap that the field can use to study myeloid cells and how they impact the way brain tumors respond to therapy,” Bernstein said.</p> <p>Chadi El Farran, a postdoctoral researcher in Bernstein’s lab, and Charles Couturier, a postdoctoral researcher in <a href="/node/446101">Alex Shalek’s lab</a> at the ӳ����ý and MIT, were co-first authors on the work with Miller.</p> <h2>Clustering cells</h2> <p>As a pathology resident, Miller watched treatment after treatment fail in patients with gliomas. He’d seen the difference immunotherapy made for other cancers, and wanted to know how to improve them for brain cancer.</p> <p>At the ӳ����ý, he decided to focus on myeloid cells, which make up to half of the cells in many brain tumors and can suppress the immune system, preventing immunotherapies from working well. Using single-cell RNA sequencing, which probes gene expression in individual cells, Miller and his colleagues examined nearly 200,000 cells from 85 different glioma tumors.</p> <p>To do this, the team used a different approach to single-cell analysis. Scientists typically analyze single-cell data by grouping similar cells together by gene expression related to cell type. But this approach can cause researchers to overlook features such as gene expression patterns related to a cell’s activities, which are important in myeloid cells.&nbsp;</p> <p>So the researchers used a method developed at the ӳ����ý in 2019 called <a href="https://elifesciences.org/articles/43803" target="_blank">consensus non-negative matrix factorization (cNMF)</a>, which can define cells by their identity and activity independently. With this approach, the team identified four programs shaping the immune system. In two, the immune system was inflammatory; it was activated and potentially trying to attack the tumor. The other two programs, found in advanced tumors, were immunosuppressive, partially shutting down the immune system and hampering its ability to fight cancer.</p> <h2>Treatment insights</h2> <p>One of the immunosuppressive programs appeared in patients who had been treated with dexamethasone, a steroid often used to reduce swelling in the brain when a patient first develops symptoms and before they receive immunotherapy. Though scientists knew that dexamethasone is immunosuppressive, they’d previously thought this was primarily due to the medication’s effects on T cells. But the new findings suggest that the drug also strongly impacts myeloid cells, and that dexamethasone should be prescribed more sparingly to improve the efficacy of immunotherapies.</p> <p>“We hope this will spur additional studies to identify ways to tackle edema [brain swelling] using different drugs and also to think about how we design clinical trials based on those results,” Miller said.</p> <p>He and his colleagues also created organoids, or three-dimensional assemblies of cells in the lab, from pieces of patient tumors, and treated the cultures with dexamethasone. They found that myeloid cells in the organoids continued to express the immunosuppressive programs long after they’d removed the drug, suggesting that the steroid could affect immunotherapy response even if only given to patients for a short time.&nbsp;</p> <p>Using the organoids, the researchers also found that cell signaling molecules such as the inflammatory protein IL-1β and the growth factor TGF-β pushed the tumors to express the other immunosuppressive cell program.&nbsp;</p> <p>Miller says scientists could one day manipulate the four programs with drugs to make immunotherapies more effective. In the meantime, he hopes that their approach highlights the importance of considering myeloid cells and will inspire other groups to study their roles in other tumors and patient populations.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the Brain Tumour Charity, the American Brain Tumor Association, The Brilliant Night Foundation, the National Institutes of Health, the Ludwig Center at Harvard, and the Emerson Collective.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Miller TE, El Farran CA, Couturier CP et al. <a href="https://www.nature.com/articles/s41586-025-08633-8" target="_blank">Programs, origins and immunomodulatory functions of myeloid cells in glioma</a>. <em>Nature</em>. Online February 26, 2025. DOI: 10.1038/s41586-025-08633-8.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/single-cell" hreflang="en">Single Cell</a></div> <div class="field__item"><a href="/broad-tags/brad-bernstein" hreflang="en">Brad Bernstein</a></div> </div> </div> </div> </div> </div> Mon, 19 Sep 2022 14:53:09 +0000 kzusi@broadinstitute.org 1195701 at /news/study-cancer-immunotherapy-patients-reveals-markers-treatment-response <span class="field field--name-title field--type-string field--label-hidden"><h1>Why brain cancer is often resistant to immunotherapy</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-02-26T11:00:00-05:00" class="datetime">February 26, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Why brain cancer is often resistant to immunotherapy</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers find four coordinated gene expression programs in immune cells from glioma tumors, including two that could lead to immunotherapy resistance.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-02-26T11:00:00-05:00" title="Wednesday, February 26, 2025 - 11:00" class="datetime">February 26, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/news/images/2022/DMG.jpeg?itok=fzytTJnT 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/news/images/2022/DMG.jpeg?itok=fzytTJnT 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/news/images/2022/DMG.jpeg?itok=X4LKDbZu 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/news/images/2022/DMG.jpeg?itok=GnO45Je- 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/news/images/2022/DMG.jpeg?itok=52daQv6W 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/news/images/2022/DMG.jpeg?itok=lEP_noFu 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/news/images/2022/DMG.jpeg?itok=lEP_noFu" alt="MRI of a diffuse midline glioma" title="MRI of a diffuse midline glioma" typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Case courtesy of Dr. Jeremy Jones, radiopaedia.org. From the case rID: 68487 </div> <div class="media-caption__description"> MRI of a diffuse midline glioma </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/623/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use 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block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/single-cell-study-childhood-brain-tumor-affirms-importance-context" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/single-cell-study-childhood-brain-tumor-affirms-importance-context"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=eNugrUoW 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=eNugrUoW 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=hv_xiYhy 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=hv_xiYhy 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=HE-WuXIF 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=nlW3AR-k 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" width="220" height="186" 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href="/news/researchers-identify-source-brain-cancers-deadly-transformation"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=UGgbAdBO 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=UGgbAdBO 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=7HxK5LZ1 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=7HxK5LZ1 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=8bYlfLPg 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=lU9aN5g2 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=lU9aN5g2" alt="Microscopy image shows glioma tumor cells in blue and pink." title="Microscopy image shows glioma tumor cells in blue and pink." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-source-brain-cancers-deadly-transformation" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify source of a brain cancer’s deadly transformation</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Immunotherapy has revolutionized the treatment of many cancers, but brain tumors such as gliomas remain particularly difficult to treat, in part because they potently suppress immune responses.</p> <p>New findings from researchers at the ӳ����ý of MIT and Harvard and the Dana-Farber Cancer Institute (DFCI) could help make immunotherapies for brain cancer more effective.</p> <p>The team analyzed almost 200,000 individual immune cells called myeloid cells from tumor samples from patients with glioma, the most common and aggressive type of primary brain cancer. In a new study in <em><a href="https://www.nature.com/articles/s41586-025-08633-8" target="_blank">Nature</a></em>, the researchers found four gene expression “programs” — sets of genes with coordinated activity — that either suppress the immune system or make it more active. They also found that patients treated with dexamethasone, a common treatment for brain cancer patients, showed signs of one of the immunosuppressive programs, suggesting that this drug could reduce the effectiveness of immunotherapy.</p> <p>The team says that defining and understanding what drives these programs could one day help researchers target them with new drugs to dial up or down specific parts of the immune system to improve patient response to immunotherapy.</p> <p>“This study provides us with the data we need to create myeloid-targeting strategies to modulate these programs and make immunotherapies more effective for brain tumor patients,” said Tyler Miller, co-first author on the study and a resident in clinical pathology at Massachusetts General Hospital when the study began.</p> <p><a href="/node/4552">Bradley Bernstein</a>, an institute member at the ӳ����ý and chair of the cancer biology department at DFCI, was the study’s senior author.</p> <p>“These gene signatures provide a roadmap that the field can use to study myeloid cells and how they impact the way brain tumors respond to therapy,” Bernstein said.</p> <p>Chadi El Farran, a postdoctoral researcher in Bernstein’s lab, and Charles Couturier, a postdoctoral researcher in <a href="/node/446101">Alex Shalek’s lab</a> at the ӳ����ý and MIT, were co-first authors on the work with Miller.</p> <h2>Clustering cells</h2> <p>As a pathology resident, Miller watched treatment after treatment fail in patients with gliomas. He’d seen the difference immunotherapy made for other cancers, and wanted to know how to improve them for brain cancer.</p> <p>At the ӳ����ý, he decided to focus on myeloid cells, which make up to half of the cells in many brain tumors and can suppress the immune system, preventing immunotherapies from working well. Using single-cell RNA sequencing, which probes gene expression in individual cells, Miller and his colleagues examined nearly 200,000 cells from 85 different glioma tumors.</p> <p>To do this, the team used a different approach to single-cell analysis. Scientists typically analyze single-cell data by grouping similar cells together by gene expression related to cell type. But this approach can cause researchers to overlook features such as gene expression patterns related to a cell’s activities, which are important in myeloid cells.&nbsp;</p> <p>So the researchers used a method developed at the ӳ����ý in 2019 called <a href="https://elifesciences.org/articles/43803" target="_blank">consensus non-negative matrix factorization (cNMF)</a>, which can define cells by their identity and activity independently. With this approach, the team identified four programs shaping the immune system. In two, the immune system was inflammatory; it was activated and potentially trying to attack the tumor. The other two programs, found in advanced tumors, were immunosuppressive, partially shutting down the immune system and hampering its ability to fight cancer.</p> <h2>Treatment insights</h2> <p>One of the immunosuppressive programs appeared in patients who had been treated with dexamethasone, a steroid often used to reduce swelling in the brain when a patient first develops symptoms and before they receive immunotherapy. Though scientists knew that dexamethasone is immunosuppressive, they’d previously thought this was primarily due to the medication’s effects on T cells. But the new findings suggest that the drug also strongly impacts myeloid cells, and that dexamethasone should be prescribed more sparingly to improve the efficacy of immunotherapies.</p> <p>“We hope this will spur additional studies to identify ways to tackle edema [brain swelling] using different drugs and also to think about how we design clinical trials based on those results,” Miller said.</p> <p>He and his colleagues also created organoids, or three-dimensional assemblies of cells in the lab, from pieces of patient tumors, and treated the cultures with dexamethasone. They found that myeloid cells in the organoids continued to express the immunosuppressive programs long after they’d removed the drug, suggesting that the steroid could affect immunotherapy response even if only given to patients for a short time.&nbsp;</p> <p>Using the organoids, the researchers also found that cell signaling molecules such as the inflammatory protein IL-1β and the growth factor TGF-β pushed the tumors to express the other immunosuppressive cell program.&nbsp;</p> <p>Miller says scientists could one day manipulate the four programs with drugs to make immunotherapies more effective. In the meantime, he hopes that their approach highlights the importance of considering myeloid cells and will inspire other groups to study their roles in other tumors and patient populations.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the Brain Tumour Charity, the American Brain Tumor Association, The Brilliant Night Foundation, the National Institutes of Health, the Ludwig Center at Harvard, and the Emerson Collective.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Miller TE, El Farran CA, Couturier CP et al. <a href="https://www.nature.com/articles/s41586-025-08633-8" target="_blank">Programs, origins and immunomodulatory functions of myeloid cells in glioma</a>. <em>Nature</em>. Online February 26, 2025. DOI: 10.1038/s41586-025-08633-8.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/single-cell" hreflang="en">Single Cell</a></div> <div class="field__item"><a href="/broad-tags/brad-bernstein" hreflang="en">Brad Bernstein</a></div> </div> </div> </div> </div> </div> Mon, 12 Sep 2022 15:06:37 +0000 adicorat 1176511 at /news/new-study-shows-how-microglia-are-prompted-change-their-state-adapt-different-areas-brain <span class="field field--name-title field--type-string field--label-hidden"><h1>Why brain cancer is often resistant to immunotherapy</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-02-26T11:00:00-05:00" class="datetime">February 26, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Why brain cancer is often resistant to immunotherapy</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers find four coordinated gene expression programs in immune cells from glioma tumors, including two that could lead to immunotherapy resistance.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-02-26T11:00:00-05:00" title="Wednesday, February 26, 2025 - 11:00" class="datetime">February 26, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/news/images/2022/DMG.jpeg?itok=fzytTJnT 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/news/images/2022/DMG.jpeg?itok=fzytTJnT 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/news/images/2022/DMG.jpeg?itok=X4LKDbZu 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/news/images/2022/DMG.jpeg?itok=GnO45Je- 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/news/images/2022/DMG.jpeg?itok=52daQv6W 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/news/images/2022/DMG.jpeg?itok=lEP_noFu 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/news/images/2022/DMG.jpeg?itok=lEP_noFu" alt="MRI of a diffuse midline glioma" title="MRI of a diffuse midline glioma" typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Case courtesy of Dr. Jeremy Jones, radiopaedia.org. From the case rID: 68487 </div> <div class="media-caption__description"> MRI of a diffuse midline glioma </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/623/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use 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field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/single-cell-study-childhood-brain-tumor-affirms-importance-context"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=eNugrUoW 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=eNugrUoW 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=hv_xiYhy 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=hv_xiYhy 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=HE-WuXIF 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=nlW3AR-k 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=nlW3AR-k" alt="Lauren Solomon, ӳ����ý Communications" typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/single-cell-study-childhood-brain-tumor-affirms-importance-context" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Single-cell study in a childhood brain tumor affirms the importance of context</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/researchers-identify-source-brain-cancers-deadly-transformation" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-identify-source-brain-cancers-deadly-transformation"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=UGgbAdBO 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=UGgbAdBO 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=7HxK5LZ1 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=7HxK5LZ1 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=8bYlfLPg 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=lU9aN5g2 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=lU9aN5g2" alt="Microscopy image shows glioma tumor cells in blue and pink." title="Microscopy image shows glioma tumor cells in blue and pink." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-source-brain-cancers-deadly-transformation" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify source of a brain cancer’s deadly transformation</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Immunotherapy has revolutionized the treatment of many cancers, but brain tumors such as gliomas remain particularly difficult to treat, in part because they potently suppress immune responses.</p> <p>New findings from researchers at the ӳ����ý of MIT and Harvard and the Dana-Farber Cancer Institute (DFCI) could help make immunotherapies for brain cancer more effective.</p> <p>The team analyzed almost 200,000 individual immune cells called myeloid cells from tumor samples from patients with glioma, the most common and aggressive type of primary brain cancer. In a new study in <em><a href="https://www.nature.com/articles/s41586-025-08633-8" target="_blank">Nature</a></em>, the researchers found four gene expression “programs” — sets of genes with coordinated activity — that either suppress the immune system or make it more active. They also found that patients treated with dexamethasone, a common treatment for brain cancer patients, showed signs of one of the immunosuppressive programs, suggesting that this drug could reduce the effectiveness of immunotherapy.</p> <p>The team says that defining and understanding what drives these programs could one day help researchers target them with new drugs to dial up or down specific parts of the immune system to improve patient response to immunotherapy.</p> <p>“This study provides us with the data we need to create myeloid-targeting strategies to modulate these programs and make immunotherapies more effective for brain tumor patients,” said Tyler Miller, co-first author on the study and a resident in clinical pathology at Massachusetts General Hospital when the study began.</p> <p><a href="/node/4552">Bradley Bernstein</a>, an institute member at the ӳ����ý and chair of the cancer biology department at DFCI, was the study’s senior author.</p> <p>“These gene signatures provide a roadmap that the field can use to study myeloid cells and how they impact the way brain tumors respond to therapy,” Bernstein said.</p> <p>Chadi El Farran, a postdoctoral researcher in Bernstein’s lab, and Charles Couturier, a postdoctoral researcher in <a href="/node/446101">Alex Shalek’s lab</a> at the ӳ����ý and MIT, were co-first authors on the work with Miller.</p> <h2>Clustering cells</h2> <p>As a pathology resident, Miller watched treatment after treatment fail in patients with gliomas. He’d seen the difference immunotherapy made for other cancers, and wanted to know how to improve them for brain cancer.</p> <p>At the ӳ����ý, he decided to focus on myeloid cells, which make up to half of the cells in many brain tumors and can suppress the immune system, preventing immunotherapies from working well. Using single-cell RNA sequencing, which probes gene expression in individual cells, Miller and his colleagues examined nearly 200,000 cells from 85 different glioma tumors.</p> <p>To do this, the team used a different approach to single-cell analysis. Scientists typically analyze single-cell data by grouping similar cells together by gene expression related to cell type. But this approach can cause researchers to overlook features such as gene expression patterns related to a cell’s activities, which are important in myeloid cells.&nbsp;</p> <p>So the researchers used a method developed at the ӳ����ý in 2019 called <a href="https://elifesciences.org/articles/43803" target="_blank">consensus non-negative matrix factorization (cNMF)</a>, which can define cells by their identity and activity independently. With this approach, the team identified four programs shaping the immune system. In two, the immune system was inflammatory; it was activated and potentially trying to attack the tumor. The other two programs, found in advanced tumors, were immunosuppressive, partially shutting down the immune system and hampering its ability to fight cancer.</p> <h2>Treatment insights</h2> <p>One of the immunosuppressive programs appeared in patients who had been treated with dexamethasone, a steroid often used to reduce swelling in the brain when a patient first develops symptoms and before they receive immunotherapy. Though scientists knew that dexamethasone is immunosuppressive, they’d previously thought this was primarily due to the medication’s effects on T cells. But the new findings suggest that the drug also strongly impacts myeloid cells, and that dexamethasone should be prescribed more sparingly to improve the efficacy of immunotherapies.</p> <p>“We hope this will spur additional studies to identify ways to tackle edema [brain swelling] using different drugs and also to think about how we design clinical trials based on those results,” Miller said.</p> <p>He and his colleagues also created organoids, or three-dimensional assemblies of cells in the lab, from pieces of patient tumors, and treated the cultures with dexamethasone. They found that myeloid cells in the organoids continued to express the immunosuppressive programs long after they’d removed the drug, suggesting that the steroid could affect immunotherapy response even if only given to patients for a short time.&nbsp;</p> <p>Using the organoids, the researchers also found that cell signaling molecules such as the inflammatory protein IL-1β and the growth factor TGF-β pushed the tumors to express the other immunosuppressive cell program.&nbsp;</p> <p>Miller says scientists could one day manipulate the four programs with drugs to make immunotherapies more effective. In the meantime, he hopes that their approach highlights the importance of considering myeloid cells and will inspire other groups to study their roles in other tumors and patient populations.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the Brain Tumour Charity, the American Brain Tumor Association, The Brilliant Night Foundation, the National Institutes of Health, the Ludwig Center at Harvard, and the Emerson Collective.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Miller TE, El Farran CA, Couturier CP et al. <a href="https://www.nature.com/articles/s41586-025-08633-8" target="_blank">Programs, origins and immunomodulatory functions of myeloid cells in glioma</a>. <em>Nature</em>. Online February 26, 2025. DOI: 10.1038/s41586-025-08633-8.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/single-cell" hreflang="en">Single Cell</a></div> <div class="field__item"><a href="/broad-tags/brad-bernstein" hreflang="en">Brad Bernstein</a></div> </div> </div> </div> </div> </div> Wed, 10 Aug 2022 21:47:28 +0000 kzusi@broadinstitute.org 1161661 at /news/molecular-map-reveals-insights-genetic-drivers-chronic-lymphocytic-leukemia <span class="field field--name-title field--type-string field--label-hidden"><h1>Why brain cancer is often resistant to immunotherapy</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-02-26T11:00:00-05:00" class="datetime">February 26, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Why brain cancer is often resistant to immunotherapy</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers find four coordinated gene expression programs in immune cells from glioma tumors, including two that could lead to immunotherapy resistance.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-02-26T11:00:00-05:00" title="Wednesday, February 26, 2025 - 11:00" class="datetime">February 26, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/news/images/2022/DMG.jpeg?itok=fzytTJnT 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/news/images/2022/DMG.jpeg?itok=fzytTJnT 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/news/images/2022/DMG.jpeg?itok=X4LKDbZu 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/news/images/2022/DMG.jpeg?itok=GnO45Je- 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/news/images/2022/DMG.jpeg?itok=52daQv6W 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/news/images/2022/DMG.jpeg?itok=lEP_noFu 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/news/images/2022/DMG.jpeg?itok=lEP_noFu" alt="MRI of a diffuse midline glioma" title="MRI of a diffuse midline glioma" typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Case courtesy of Dr. Jeremy Jones, radiopaedia.org. From the case rID: 68487 </div> <div class="media-caption__description"> MRI of a diffuse midline glioma </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/623/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use 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field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/single-cell-study-childhood-brain-tumor-affirms-importance-context"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=eNugrUoW 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=eNugrUoW 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=hv_xiYhy 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=hv_xiYhy 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=HE-WuXIF 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=nlW3AR-k 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=nlW3AR-k" alt="Lauren Solomon, ӳ����ý Communications" typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/single-cell-study-childhood-brain-tumor-affirms-importance-context" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Single-cell study in a childhood brain tumor affirms the importance of context</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/researchers-identify-source-brain-cancers-deadly-transformation" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-identify-source-brain-cancers-deadly-transformation"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=UGgbAdBO 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=UGgbAdBO 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=7HxK5LZ1 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=7HxK5LZ1 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=8bYlfLPg 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=lU9aN5g2 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=lU9aN5g2" alt="Microscopy image shows glioma tumor cells in blue and pink." title="Microscopy image shows glioma tumor cells in blue and pink." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-source-brain-cancers-deadly-transformation" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify source of a brain cancer’s deadly transformation</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Immunotherapy has revolutionized the treatment of many cancers, but brain tumors such as gliomas remain particularly difficult to treat, in part because they potently suppress immune responses.</p> <p>New findings from researchers at the ӳ����ý of MIT and Harvard and the Dana-Farber Cancer Institute (DFCI) could help make immunotherapies for brain cancer more effective.</p> <p>The team analyzed almost 200,000 individual immune cells called myeloid cells from tumor samples from patients with glioma, the most common and aggressive type of primary brain cancer. In a new study in <em><a href="https://www.nature.com/articles/s41586-025-08633-8" target="_blank">Nature</a></em>, the researchers found four gene expression “programs” — sets of genes with coordinated activity — that either suppress the immune system or make it more active. They also found that patients treated with dexamethasone, a common treatment for brain cancer patients, showed signs of one of the immunosuppressive programs, suggesting that this drug could reduce the effectiveness of immunotherapy.</p> <p>The team says that defining and understanding what drives these programs could one day help researchers target them with new drugs to dial up or down specific parts of the immune system to improve patient response to immunotherapy.</p> <p>“This study provides us with the data we need to create myeloid-targeting strategies to modulate these programs and make immunotherapies more effective for brain tumor patients,” said Tyler Miller, co-first author on the study and a resident in clinical pathology at Massachusetts General Hospital when the study began.</p> <p><a href="/node/4552">Bradley Bernstein</a>, an institute member at the ӳ����ý and chair of the cancer biology department at DFCI, was the study’s senior author.</p> <p>“These gene signatures provide a roadmap that the field can use to study myeloid cells and how they impact the way brain tumors respond to therapy,” Bernstein said.</p> <p>Chadi El Farran, a postdoctoral researcher in Bernstein’s lab, and Charles Couturier, a postdoctoral researcher in <a href="/node/446101">Alex Shalek’s lab</a> at the ӳ����ý and MIT, were co-first authors on the work with Miller.</p> <h2>Clustering cells</h2> <p>As a pathology resident, Miller watched treatment after treatment fail in patients with gliomas. He’d seen the difference immunotherapy made for other cancers, and wanted to know how to improve them for brain cancer.</p> <p>At the ӳ����ý, he decided to focus on myeloid cells, which make up to half of the cells in many brain tumors and can suppress the immune system, preventing immunotherapies from working well. Using single-cell RNA sequencing, which probes gene expression in individual cells, Miller and his colleagues examined nearly 200,000 cells from 85 different glioma tumors.</p> <p>To do this, the team used a different approach to single-cell analysis. Scientists typically analyze single-cell data by grouping similar cells together by gene expression related to cell type. But this approach can cause researchers to overlook features such as gene expression patterns related to a cell’s activities, which are important in myeloid cells.&nbsp;</p> <p>So the researchers used a method developed at the ӳ����ý in 2019 called <a href="https://elifesciences.org/articles/43803" target="_blank">consensus non-negative matrix factorization (cNMF)</a>, which can define cells by their identity and activity independently. With this approach, the team identified four programs shaping the immune system. In two, the immune system was inflammatory; it was activated and potentially trying to attack the tumor. The other two programs, found in advanced tumors, were immunosuppressive, partially shutting down the immune system and hampering its ability to fight cancer.</p> <h2>Treatment insights</h2> <p>One of the immunosuppressive programs appeared in patients who had been treated with dexamethasone, a steroid often used to reduce swelling in the brain when a patient first develops symptoms and before they receive immunotherapy. Though scientists knew that dexamethasone is immunosuppressive, they’d previously thought this was primarily due to the medication’s effects on T cells. But the new findings suggest that the drug also strongly impacts myeloid cells, and that dexamethasone should be prescribed more sparingly to improve the efficacy of immunotherapies.</p> <p>“We hope this will spur additional studies to identify ways to tackle edema [brain swelling] using different drugs and also to think about how we design clinical trials based on those results,” Miller said.</p> <p>He and his colleagues also created organoids, or three-dimensional assemblies of cells in the lab, from pieces of patient tumors, and treated the cultures with dexamethasone. They found that myeloid cells in the organoids continued to express the immunosuppressive programs long after they’d removed the drug, suggesting that the steroid could affect immunotherapy response even if only given to patients for a short time.&nbsp;</p> <p>Using the organoids, the researchers also found that cell signaling molecules such as the inflammatory protein IL-1β and the growth factor TGF-β pushed the tumors to express the other immunosuppressive cell program.&nbsp;</p> <p>Miller says scientists could one day manipulate the four programs with drugs to make immunotherapies more effective. In the meantime, he hopes that their approach highlights the importance of considering myeloid cells and will inspire other groups to study their roles in other tumors and patient populations.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the Brain Tumour Charity, the American Brain Tumor Association, The Brilliant Night Foundation, the National Institutes of Health, the Ludwig Center at Harvard, and the Emerson Collective.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Miller TE, El Farran CA, Couturier CP et al. <a href="https://www.nature.com/articles/s41586-025-08633-8" target="_blank">Programs, origins and immunomodulatory functions of myeloid cells in glioma</a>. <em>Nature</em>. Online February 26, 2025. DOI: 10.1038/s41586-025-08633-8.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/single-cell" hreflang="en">Single Cell</a></div> <div class="field__item"><a href="/broad-tags/brad-bernstein" hreflang="en">Brad Bernstein</a></div> </div> </div> </div> </div> </div> Thu, 04 Aug 2022 16:53:54 +0000 kzusi@broadinstitute.org 1157391 at /news/single-cell-map-heart-failure-suggests-possible-therapeutic-targets <span class="field field--name-title field--type-string field--label-hidden"><h1>Why brain cancer is often resistant to immunotherapy</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Allessandra DiCorato</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-02-26T11:00:00-05:00" class="datetime">February 26, 2025</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Why brain cancer is often resistant to immunotherapy</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>Researchers find four coordinated gene expression programs in immune cells from glioma tumors, including two that could lead to immunotherapy resistance.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Allessandra DiCorato </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-02-26T11:00:00-05:00" title="Wednesday, February 26, 2025 - 11:00" class="datetime">February 26, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/news/images/2022/DMG.jpeg?itok=fzytTJnT 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/news/images/2022/DMG.jpeg?itok=fzytTJnT 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"> <source srcset="/files/styles/multiple_ct_header_desktop/public/news/images/2022/DMG.jpeg?itok=X4LKDbZu 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"> <source srcset="/files/styles/multiple_ct_header_laptop/public/news/images/2022/DMG.jpeg?itok=GnO45Je- 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"> <source srcset="/files/styles/multiple_ct_header_tablet/public/news/images/2022/DMG.jpeg?itok=52daQv6W 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"> <source srcset="/files/styles/multiple_ct_header_phone/public/news/images/2022/DMG.jpeg?itok=lEP_noFu 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/news/images/2022/DMG.jpeg?itok=lEP_noFu" alt="MRI of a diffuse midline glioma" title="MRI of a diffuse midline glioma" typeof="foaf:Image"> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Case courtesy of Dr. Jeremy Jones, radiopaedia.org. From the case rID: 68487 </div> <div class="media-caption__description"> MRI of a diffuse midline glioma </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous"></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/623/feed&amp;title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use 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field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/single-cell-study-childhood-brain-tumor-affirms-importance-context"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=eNugrUoW 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=eNugrUoW 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=hv_xiYhy 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=hv_xiYhy 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=HE-WuXIF 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2018/Gliomas_main_v4B.jpg?h=d3e04ee7&amp;itok=nlW3AR-k 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" width="220" height="186" 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href="/news/researchers-identify-source-brain-cancers-deadly-transformation"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=UGgbAdBO 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=UGgbAdBO 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=7HxK5LZ1 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=7HxK5LZ1 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=8bYlfLPg 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=lU9aN5g2 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/32446414167_c546eaaeb3_k%20%281%29.jpg?h=bce46435&amp;itok=lU9aN5g2" alt="Microscopy image shows glioma tumor cells in blue and pink." title="Microscopy image shows glioma tumor cells in blue and pink." typeof="foaf:Image"> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-source-brain-cancers-deadly-transformation" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify source of a brain cancer’s deadly transformation</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Immunotherapy has revolutionized the treatment of many cancers, but brain tumors such as gliomas remain particularly difficult to treat, in part because they potently suppress immune responses.</p> <p>New findings from researchers at the ӳ����ý of MIT and Harvard and the Dana-Farber Cancer Institute (DFCI) could help make immunotherapies for brain cancer more effective.</p> <p>The team analyzed almost 200,000 individual immune cells called myeloid cells from tumor samples from patients with glioma, the most common and aggressive type of primary brain cancer. In a new study in <em><a href="https://www.nature.com/articles/s41586-025-08633-8" target="_blank">Nature</a></em>, the researchers found four gene expression “programs” — sets of genes with coordinated activity — that either suppress the immune system or make it more active. They also found that patients treated with dexamethasone, a common treatment for brain cancer patients, showed signs of one of the immunosuppressive programs, suggesting that this drug could reduce the effectiveness of immunotherapy.</p> <p>The team says that defining and understanding what drives these programs could one day help researchers target them with new drugs to dial up or down specific parts of the immune system to improve patient response to immunotherapy.</p> <p>“This study provides us with the data we need to create myeloid-targeting strategies to modulate these programs and make immunotherapies more effective for brain tumor patients,” said Tyler Miller, co-first author on the study and a resident in clinical pathology at Massachusetts General Hospital when the study began.</p> <p><a href="/node/4552">Bradley Bernstein</a>, an institute member at the ӳ����ý and chair of the cancer biology department at DFCI, was the study’s senior author.</p> <p>“These gene signatures provide a roadmap that the field can use to study myeloid cells and how they impact the way brain tumors respond to therapy,” Bernstein said.</p> <p>Chadi El Farran, a postdoctoral researcher in Bernstein’s lab, and Charles Couturier, a postdoctoral researcher in <a href="/node/446101">Alex Shalek’s lab</a> at the ӳ����ý and MIT, were co-first authors on the work with Miller.</p> <h2>Clustering cells</h2> <p>As a pathology resident, Miller watched treatment after treatment fail in patients with gliomas. He’d seen the difference immunotherapy made for other cancers, and wanted to know how to improve them for brain cancer.</p> <p>At the ӳ����ý, he decided to focus on myeloid cells, which make up to half of the cells in many brain tumors and can suppress the immune system, preventing immunotherapies from working well. Using single-cell RNA sequencing, which probes gene expression in individual cells, Miller and his colleagues examined nearly 200,000 cells from 85 different glioma tumors.</p> <p>To do this, the team used a different approach to single-cell analysis. Scientists typically analyze single-cell data by grouping similar cells together by gene expression related to cell type. But this approach can cause researchers to overlook features such as gene expression patterns related to a cell’s activities, which are important in myeloid cells.&nbsp;</p> <p>So the researchers used a method developed at the ӳ����ý in 2019 called <a href="https://elifesciences.org/articles/43803" target="_blank">consensus non-negative matrix factorization (cNMF)</a>, which can define cells by their identity and activity independently. With this approach, the team identified four programs shaping the immune system. In two, the immune system was inflammatory; it was activated and potentially trying to attack the tumor. The other two programs, found in advanced tumors, were immunosuppressive, partially shutting down the immune system and hampering its ability to fight cancer.</p> <h2>Treatment insights</h2> <p>One of the immunosuppressive programs appeared in patients who had been treated with dexamethasone, a steroid often used to reduce swelling in the brain when a patient first develops symptoms and before they receive immunotherapy. Though scientists knew that dexamethasone is immunosuppressive, they’d previously thought this was primarily due to the medication’s effects on T cells. But the new findings suggest that the drug also strongly impacts myeloid cells, and that dexamethasone should be prescribed more sparingly to improve the efficacy of immunotherapies.</p> <p>“We hope this will spur additional studies to identify ways to tackle edema [brain swelling] using different drugs and also to think about how we design clinical trials based on those results,” Miller said.</p> <p>He and his colleagues also created organoids, or three-dimensional assemblies of cells in the lab, from pieces of patient tumors, and treated the cultures with dexamethasone. They found that myeloid cells in the organoids continued to express the immunosuppressive programs long after they’d removed the drug, suggesting that the steroid could affect immunotherapy response even if only given to patients for a short time.&nbsp;</p> <p>Using the organoids, the researchers also found that cell signaling molecules such as the inflammatory protein IL-1β and the growth factor TGF-β pushed the tumors to express the other immunosuppressive cell program.&nbsp;</p> <p>Miller says scientists could one day manipulate the four programs with drugs to make immunotherapies more effective. In the meantime, he hopes that their approach highlights the importance of considering myeloid cells and will inspire other groups to study their roles in other tumors and patient populations.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported in part by the Brain Tumour Charity, the American Brain Tumor Association, The Brilliant Night Foundation, the National Institutes of Health, the Ludwig Center at Harvard, and the Emerson Collective.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Miller TE, El Farran CA, Couturier CP et al. <a href="https://www.nature.com/articles/s41586-025-08633-8" target="_blank">Programs, origins and immunomodulatory functions of myeloid cells in glioma</a>. <em>Nature</em>. Online February 26, 2025. DOI: 10.1038/s41586-025-08633-8.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/cancer" hreflang="en">Cancer</a></div> <div class="field__item"><a href="/broad-tags/single-cell" hreflang="en">Single Cell</a></div> <div class="field__item"><a href="/broad-tags/brad-bernstein" hreflang="en">Brad Bernstein</a></div> </div> </div> </div> </div> </div> Wed, 22 Jun 2022 18:03:24 +0000 adicorat 1136501 at