in Colorectal Cancer Relates to Immune Response Differentially by Tumor Microsatellite Instability Status.

The presence of () in colorectal carcinoma tissue has been associated with microsatellite instability (MSI), lower-level T-cell infiltrates, and poor clinical outcomes. Considering differences in the tumor-immune microenvironment between MSI-high and non-MSI-high carcinomas, we hypothesized that the association of with immune response might differ by tumor MSI status. Using samples from 1,041 rectal and colon cancer patients within the Nurses' Health Study and Health Professionals Follow-up Study, we measured DNA in tumor tissue by a quantitative polymerase chain reaction assay. Multivariable logistic regression models were used to examine the association between status and histopathologic lymphocytic reactions or density of CD3 cells, CD8 cells, CD45RO (PTPRC) cells, or FOXP3 cells in strata of tumor MSI status. We adjusted for potential confounders, including CpG island methylator phenotype; LINE-1 methylation; and , and mutations. The association of with tumor-infiltrating lymphocytes (TIL) and intratumoral periglandular reaction differed by tumor MSI status ( = 0.002). The presence of was negatively associated with TIL in MSI-high tumors [multivariable odds ratio (OR), 0.45; 95% confidence interval (CI), 0.22-0.92], but positively associated with TIL in non-MSI-high tumors (multivariable OR 1.91; 95% CI, 1.12-3.25). No significant differential association was observed for peritumoral lymphocytic reaction, Crohn-like lymphoid reaction, or T-cell densities. In conclusion, the association of with immune response to colorectal carcinoma differs by tumor MSI status, suggesting that and MSI status interact to affect antitumor immune reactions. .