Dataset Information

Inverse relationship between Fusobacterium nucleatum amount and tumor CD274 (PD-L1) expression in colorectal carcinoma.

ABSTRACT:

Objectives

The CD274 (programmed cell death 1 ligand 1, PD-L1)/PDCD1 (programmed cell death 1, PD-1) immune checkpoint axis is known to regulate the antitumor immune response. Evidence also supports an immunosuppressive effect of Fusobacterium nucleatum. We hypothesised that tumor CD274 overexpression might be inversely associated with abundance of F. nucleatum in colorectal carcinoma.

Methods

We assessed tumor CD274 expression by immunohistochemistry and F. nucleatum DNA within tumor tissue by quantitative PCR in 812 cases among 4465 incident rectal and colon cancer cases that had occurred in two prospective cohort studies. Multivariable logistic regression analyses with inverse probability weighting were used to adjust for selection bias because of tissue data availability and potential confounders including microsatellite instability status, CpG island methylator phenotype, LINE-1 methylation level and KRAS, BRAF and PIK3CA mutations.

Results

Fusobacterium nucleatum DNA was detected in tumor tissue in 109 (13%) cases. Tumor CD274 expression level was inversely associated with the amount of F. nucleatum in colorectal cancer tissue (P = 0.0077). For one category-unit increase in three ordinal F. nucleatum categories (negative vs. low vs. high), multivariable-adjusted odds ratios (with 95% confidence interval) of the low, intermediate and high CD274 categories (vs. negative) were 0.78 (0.41-1.51), 0.64 (0.32-1.28) and 0.50 (0.25-0.99), respectively (P _trend = 0.032).

Conclusions

Tumor CD274 expression level was inversely associated with the amount of F. nucleatum in colorectal cancer tissue, suggesting that different immunosuppressive mechanisms (i.e. PDCD1 immune checkpoint activation and tumor F. nucleatum enrichment) tend to be used by different tumor subgroups.

SUBMITTER: Ugai T

PROVIDER: S-EPMC10394676 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Publications

Inverse relationship between <i>Fusobacterium nucleatum</i> amount and tumor CD274 (PD-L1) expression in colorectal carcinoma.

Ugai Tomotaka T Shimizu Takashi T Kawamura Hidetaka H Ugai Satoko S Takashima Yasutoshi Y Usui Genki G Väyrynen Juha P JP Okadome Kazuo K Haruki Koichiro K Akimoto Naohiko N Masugi Yohei Y da Silva Annacarolina A Mima Kosuke K Zhang Xuehong X Chan Andrew T AT Wang Molin M Garrett Wendy S WS Freeman Gordon J GJ Meyerhardt Jeffrey A JA Nowak Jonathan A JA Song Mingyang M Giannakis Marios M Ogino Shuji S

Clinical & translational immunology 20230802 8

<h4>Objectives</h4>The CD274 (programmed cell death 1 ligand 1, PD-L1)/PDCD1 (programmed cell death 1, PD-1) immune checkpoint axis is known to regulate the antitumor immune response. Evidence also supports an immunosuppressive effect of <i>Fusobacterium nucleatum</i>. We hypothesised that tumor CD274 overexpression might be inversely associated with abundance of <i>F. nucleatum</i> in colorectal carcinoma.<h4>Methods</h4>We assessed tumor CD274 expression by immunohistochemistry and <i>F. nucle ...[more]

PMID: 37538192

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