Fusobacterium Nucleatum Enhances the Efficacy of PD-L1 Blockade in Colorectal Cancer

Overview

Journal Signal Transduct Target Ther

Specialties Cell Biology
Pharmacology

Date 2021 Nov 19

PMID 34795206

Citations 97

Authors

Yaohui Gao

Dexi Bi

Ruting Xie

Man Li

Jing Guo

Hu Liu

Xianling Guo

Juemin Fang

Tingting Ding

Huiyuan Zhu

Yuan Cao

Meichun Xing

Jiayi Zheng

Qing Xu

Qian Xu

Qing Wei

Huanlong Qin

Affiliations

Soon will be listed here.

Abstract

Given that only a subset of patients with colorectal cancer (CRC) benefit from immune checkpoint therapy, efforts are ongoing to identify markers that predict immunotherapeutic response. Increasing evidence suggests that microbes influence the efficacy of cancer therapies. Fusobacterium nucleatum induces different immune responses in CRC with different microsatellite-instability (MSI) statuses. Here, we investigated the effect of F. nucleatum on anti-PD-L1 therapy in CRC. We found that high F. nucleatum levels correlate with improved therapeutic responses to PD-1 blockade in patients with CRC. Additionally, F. nucleatum enhanced the antitumor effects of PD-L1 blockade on CRC in mice and prolonged survival. Combining F. nucleatum supplementation with immunotherapy rescued the therapeutic effects of PD-L1 blockade. Furthermore, F. nucleatum induced PD-L1 expression by activating STING signaling and increased the accumulation of interferon-gamma (IFN-γ) CD8 tumor-infiltrating lymphocytes (TILs) during treatment with PD-L1 blockade, thereby augmenting tumor sensitivity to PD-L1 blockade. Finally, patient-derived organoid models demonstrated that increased F. nucleatum levels correlated with an improved therapeutic response to PD-L1 blockade. These findings suggest that F. nucleatum may modulate immune checkpoint therapy for CRC.

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