TY - JOUR
T1 - Fusobacterium nucleatum in colorectal cancer relates to immune response differentially by tumor microsatellite instability status
AU - Hamada, Tsuyoshi
AU - Zhang, Xuehong
AU - Mima, Kosuke
AU - Bullman, Susan
AU - Sukawa, Yasutaka
AU - Nowak, Jonathan A.
AU - Kosumi, Keisuke
AU - Masugi, Yohei
AU - Twombly, Tyler S.
AU - Cao, Yin
AU - Song, Mingyang
AU - Liu, Li
AU - da Silva, Annacarolina
AU - Shi, Yan
AU - Gu, Mancang
AU - Li, Wanwan
AU - Koh, Hideo
AU - Nosho, Katsuhiko
AU - Inamura, Kentaro
AU - Keum, Na Na
AU - Wu, Kana
AU - Meyerhardt, Jeffrey A.
AU - Kostic, Aleksandar D.
AU - Huttenhower, Curtis
AU - Garrett, Wendy S.
AU - Meyerson, Matthew
AU - Giovannucci, Edward L.
AU - Chan, Andrew T.
AU - Fuchs, Charles S.
AU - Nishihara, Reiko
AU - Giannakis, Marios
AU - Ogino, Shuji
N1 - Publisher Copyright:
©2018 American Association for Cancer Research.
PY - 2018/11
Y1 - 2018/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85065266148&partnerID=8YFLogxK
U2 - 10.1158/2326-6066.CIR-18-0174
DO - 10.1158/2326-6066.CIR-18-0174
M3 - Article
C2 - 30228205
AN - SCOPUS:85065266148
SN - 2326-6066
VL - 6
SP - 1327
EP - 1336
JO - Cancer Immunology Research
JF - Cancer Immunology Research
IS - 11
ER -