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

Cancer Immunol Res
Authors
Keywords
Abstract

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. .

Year of Publication
2018
Journal
Cancer Immunol Res
Volume
6
Issue
11
Pages
1327-1336
Date Published
2018 11
ISSN
2326-6074
DOI
10.1158/2326-6066.CIR-18-0174
PubMed ID
30228205
PubMed Central ID
PMC6215508
Links
Grant list
KL2 TR001100 / TR / NCATS NIH HHS / United States
R35 CA197735 / CA / NCI NIH HHS / United States
R01 CA118553 / CA / NCI NIH HHS / United States
P01 CA087969 / CA / NCI NIH HHS / United States
P01 CA055075 / CA / NCI NIH HHS / United States
R01 CA151993 / CA / NCI NIH HHS / United States
U01 CA167552 / CA / NCI NIH HHS / United States
R01 CA137178 / CA / NCI NIH HHS / United States
P30 DK036836 / DK / NIDDK NIH HHS / United States
K24 DK098311 / DK / NIDDK NIH HHS / United States
R01 CA154426 / CA / NCI NIH HHS / United States
UM1 CA186107 / CA / NCI NIH HHS / United States
R01 CA169141 / CA / NCI NIH HHS / United States
K07 CA188126 / CA / NCI NIH HHS / United States
UM1 CA167552 / CA / NCI NIH HHS / United States
R00 CA215314 / CA / NCI NIH HHS / United States
P50 CA127003 / CA / NCI NIH HHS / United States
K07 CA190673 / CA / NCI NIH HHS / United States