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OBJECTIVES: The CD274 (programmed cell death 1 ligand 1, PD-L1)/PDCD1 (programmed cell death 1, PD-1) immune checkpoint axis is known to regulate the antitumor immune response. Evidence also supports an immunosuppressive effect of . We hypothesised that tumor CD274 overexpression might be inversely associated with abundance of in colorectal carcinoma.METHODS: We assessed tumor CD274 expression by immunohistochemistry and DNA within tumor tissue by quantitative PCR in 812 cases among 4465 incident rectal and colon cancer cases that had occurred in two prospective cohort studies. Multivariable logistic regression analyses with inverse probability weighting were used to adjust for selection bias because of tissue data availability and potential confounders including microsatellite instability status, CpG island methylator phenotype, LINE-1 methylation level and , and mutations.RESULTS: DNA was detected in tumor tissue in 109 (13%) cases. Tumor CD274 expression level was inversely associated with the amount of in colorectal cancer tissue ( = 0.0077). For one category-unit increase in three ordinal categories (negative vs. low vs. high), multivariable-adjusted odds ratios (with 95% confidence interval) of the low, intermediate and high CD274 categories (vs. negative) were 0.78 (0.41-1.51), 0.64 (0.32-1.28) and 0.50 (0.25-0.99), respectively (  = 0.032).CONCLUSIONS: Tumor CD274 expression level was inversely associated with the amount of in colorectal cancer tissue, suggesting that different immunosuppressive mechanisms (i.e. PDCD1 immune checkpoint activation and tumor enrichment) tend to be used by different tumor subgroups.