| Literature DB >> 30228205 |
Tsuyoshi Hamada1, Xuehong Zhang2, Kosuke Mima3, Susan Bullman3,4, Yasutaka Sukawa3, Jonathan A Nowak5, Keisuke Kosumi1, Yohei Masugi1, Tyler S Twombly1, Yin Cao6,7,8,9, Mingyang Song6,7,8, Li Liu1,8,10, Annacarolina da Silva1, Yan Shi1,11, Mancang Gu1,12, Wanwan Li1, Hideo Koh1, Katsuhiko Nosho13, Kentaro Inamura14, NaNa Keum8,15, Kana Wu2,8,16, Jeffrey A Meyerhardt3, Aleksandar D Kostic4,17, Curtis Huttenhower4,18, Wendy S Garrett3,4,19, Matthew Meyerson3,4, Edward L Giovannucci2,8,16, Andrew T Chan2,6,7, Charles S Fuchs20,21,22, Reiko Nishihara1,5,8,16,18, Marios Giannakis23,4,24, Shuji Ogino25,4,5,16.
Abstract
The presence of Fusobacterium nucleatum (F. nucleatum) 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 F. nucleatum 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 F. nucleatum DNA in tumor tissue by a quantitative polymerase chain reaction assay. Multivariable logistic regression models were used to examine the association between F. nucleatum 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 KRAS, BRAF, and PIK3CA mutations. The association of F. nucleatum with tumor-infiltrating lymphocytes (TIL) and intratumoral periglandular reaction differed by tumor MSI status (P interaction = 0.002). The presence of F. nucleatum 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 F. nucleatum with immune response to colorectal carcinoma differs by tumor MSI status, suggesting that F. nucleatum and MSI status interact to affect antitumor immune reactions. Cancer Immunol Res; 6(11); 1327-36. ©2018 AACR See related Spotlight on p. 1290. ©2018 American Association for Cancer Research.Entities:
Mesh：
Year: 2018 PMID： 30228205 PMCID： PMC6215508 DOI： 10.1158/2326-6066.CIR-18-0174
Source DB: PubMed Journal: Cancer Immunol Res ISSN： 2326-6066 Impact factor: 11.151