期刊
CANCER IMMUNOLOGY RESEARCH
卷 6, 期 11, 页码 1327-1336出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-18-0174
关键词
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资金
- NIH [P01 CA87969, UM1 CA186107, P01 CA55075, UM1 CA167552, U01 CA167552, P50 CA127003, R01 CA118553, R01 CA169141, R01 CA137178, K24 DK098311, R35 CA197735, R01 CA151993, K07 CA190673, K07 CA188126]
- Dana-Farber Harvard Cancer Center [2016-02]
- Project P Fund
- Friends of the Dana-Farber Cancer Institute
- Bennett Family Fund
- Entertainment Industry Foundation through National Colorectal Cancer Research Alliance
- Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant [SU2C-AACR-DT22-17]
- Mitsukoshi Health and Welfare Foundation
- Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers from Japan Society for the Promotion of Science
- Overseas Research Fellowship from Japan Society for the Promotion of Science [JP2017-775]
- Program for Advancing Strategic International Networks to Accelerate the Circulation of Talented Researchers, from Japan Society for the Promotion of Science
- AACR-AstraZeneca Fellowship in Immuno-oncology Research [17-40-12-SONG]
- Chinese Scholarship Council
- Huazhong University of Science and Technology
- National Research Foundation of Korea [NRF-2018R1C1B6008822, NRF-2018R1A4A1022589]
- KL2/Catalyst Medical Research Investigator Training award (NIH) [KL2 TR001100]
- American Association for Cancer Research, the Scientific Partner of SU2C
- NATIONAL CANCER INSTITUTE [K07CA190673, UM1CA167552, P01CA055075, P50CA127003, R01CA118553, K07CA188126, P01CA087969, R01CA154426, R35CA197735, R00CA215314, R01CA137178, R01CA169141, U01CA167552, R01CA151993, UM1CA186107] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [KL2TR001100] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [K24DK098311, P30DK036836] Funding Source: NIH RePORTER
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 antitumorimmune reactions. (C) 2018 AACR.
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