| Literature DB >> 29038297 |
Yohei Masugi1,2, Reiko Nishihara1,2,3,4,5,6, Tsuyoshi Hamada1,2, Mingyang Song4,7,8, Annacarolina da Silva1,2, Keisuke Kosumi1,2, Mancang Gu1,2, Yan Shi1,2, Wanwan Li1,2, Li Liu1,2,4,9, Daniel Nevo5,6, Kentaro Inamura10, Yin Cao4,7,8, Xiaoyun Liao1,11, Katsuhiko Nosho12, Andrew T Chan7,8,13, Marios Giannakis1,14,15, Adam J Bass1,14,15, F Stephen Hodi1,11, Gordon J Freeman1, Scott J Rodig2,16, Charles S Fuchs17,18,19, Zhi Rong Qian20,2, Jonathan A Nowak2,3, Shuji Ogino20,2,3,5.
Abstract
Expression of the immune checkpoint ligand CD274 (programmed cell death 1 ligand 1, PD-L1, from gene CD274) contributes to suppression of antitumor T cell-mediated immune response in various tumor types. However, the role of PDCD1LG2 (PD-L2, CD273, from gene PDCD1LG2) in the tumor microenvironment remains unclear. We hypothesized that tumor PDCD1LG2 expression might be inversely associated with lymphocytic reactions to colorectal cancer. We examined tumor PDCD1LG2 expression by IHC in 823 colon and rectal carcinoma cases within two U.S.-nationwide cohort studies and categorized tumors into quartiles according to the percentage of PDCD1LG2-expressing carcinoma cells. We conducted multivariable ordinal logistic regression analysis to assess the associations of tumor PDCD1LG2 expression with Crohn-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, or tumor-infiltrating lymphocytes, controlling for potential confounders, including microsatellite instability, CpG island methylator phenotype, long-interspersed nucleotide element-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Tumor PDCD1LG2 expression was inversely associated with Crohn-like lymphoid reaction (Ptrend = 0.0003). For a unit increase in the three-tiered ordinal categories of Crohn-like lymphoid reaction, a multivariable OR in the highest (vs. lowest) quartile of the percentage of PDCD1LG2-expressing tumor cells was 0.38 (95% confidence interval, 0.22-0.67). Tumor PDCD1LG2 expression was not associated with peritumoral lymphocytic reaction, intratumoral periglandular reaction, tumor-infiltrating lymphocytes, or patient survival (Ptrend > 0.13). Thus, tumor PDCD1LG2 expression is inversely associated with Crohn-like lymphoid reaction to colorectal cancer, suggesting a possible role of PDCD1LG2-expressing tumor cells in inhibiting the development of tertiary lymphoid tissues during colorectal carcinogenesis. Cancer Immunol Res; 5(11); 1046-55. ©2017 AACR. ©2017 American Association for Cancer Research.Entities:
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Year: 2017 PMID： 29038297 PMCID： PMC5668177 DOI： 10.1158/2326-6066.CIR-17-0122
Source DB: PubMed Journal: Cancer Immunol Res ISSN： 2326-6066 Impact factor: 12.020