Abstract B001: Inverse relationship between tissue fusobacterium nucleatum amount and CD274 (PD-L1) expression of colorectal carcinoma


 Background: The CD274 (programmed cell death ligand 1, PD-L1)/PDCD1 (programmed cell death 1, PD-1) immune checkpoint axis is known to regulate the antitumor immune response. Evidence suggests that Fusobacterium nucleatum (F. nucleatum) promotes colorectal carcinogenesis through its suppressive effect on antitumor immunity. We hypothesized that tumor CD274 overexpression and intratumor abundance of F. nucleatum might tend to be mutually exclusive immune evasion mechanisms in colorectal cancer. Methods: We assessed tumor CD274 expression by immunohistochemistry and F. nucleatum DNA within tumor tissue by quantitative polymerase chain reaction in 812 cases among 4,465 incident colorectal cancer cases that had occurred in the Nurses’ Health Study and the Health Professionals Follow-up Study. To adjust for potential confounders and selection bias due to tissue data availability, inverse probability weighting was integrated into multivariable ordinal logistic regression analyses to examine the association of tumor CD274 expression with the amount of intratumor F. nucleatum. Results: Tumor CD274 expression was negative in 93 (11%), low in 231 (28%), intermediate in 210 (26%), and high in 278 (34%) of 812 cases. F. nucleatum DNA was detected in tumor tissue in 109 (13%) cases of 812 cases. Tumor CD274 expression level was inversely associated with the amount of F. nucleatum in colorectal cancer tissue. For one category increase in three ordinal F. nucleatum categories (negative, low, and high), multivariable-adjusted odds ratios (with 95% confidence intervals) of the low, middle, and high CD274 expression categories (vs. negative) were 0.78 (0.41-1.51), 0.64 (0.32-1.28), and 0.50 (0.25–0.99), respectively (Ptrend=0.032). Conclusions: We found that CD274 expression was inversely associated with the amount of F. nucleatum in colorectal cancer tissue. Our findings suggest that a colorectal tumor tends to have either of the immune evasion mechanisms, i.e., PDCD1 (PD-1) immune checkpoint activation and intratumor abundance of F. nucleatum.
 Citation Format: Tomotaka Ugai, Takashi Shimizu, Hidetaka Kawamura, Yasutoshi Takashima, Juha P. Väyrynen, Seyed Mostafa Mousavi Kahaki, Kazuo Okadome, Yohei Masugi, Annacarolina da Silva, Xuehong Zhang, Andrew T. Chan, Molin Wang, Jeffrey A. Meyerhardt, Jonathan A. Nowak, Mingyang Song, Marios Giannakis, Shuji Ogino. Inverse relationship between tissue fusobacterium nucleatum amount and CD274 (PD-L1) expression of colorectal carcinoma [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr B001.