Intracellular Fusobacterium nucleatum infection attenuates antitumor immunity in esophageal squamous cell carcinoma

Yiqiu Li, Shan Xing, Fangfang Chen, Qifan Li, Shuheng Dou, Yuying Huang, Jun An (), Wanli Liu () and Ge Zhang ()
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Yiqiu Li: Sun Yat-sen University
Shan Xing: Sun Yat-sen University Cancer Center
Fangfang Chen: Sun Yat-sen University
Qifan Li: Sun Yat-sen University
Shuheng Dou: Sun Yat-sen University
Yuying Huang: Sun Yat-sen University
Jun An: Yuedong Hospital
Wanli Liu: Sun Yat-sen University Cancer Center
Ge Zhang: Sun Yat-sen University

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract Currently, the influence of the tumor microbiome on the effectiveness of immunotherapy remains largely unknown. Intratumoural Fusobacterium nucleatum (Fn) functions as an oncogenic bacterium and can promote tumor progression in esophageal squamous cell carcinoma (ESCC). Our previous study revealed that Fn is a facultative intracellular bacterium and that its virulence factor Fn-Dps facilitates the intracellular survival of Fn. In this study, we find that Fn DNA is enriched in the nonresponder (NR) group among ESCC patients receiving PD-1 inhibitor and that the serum antibody level of Fn is significantly higher in the NR group than in the responder (R) group. In addition, Fn infection has an opposite impact on the efficacy of αPD-L1 treatment in animals. Mechanistically, we confirm that Fn can inhibit the proliferation and cytokine secretion of T cells and that Fn-Dps binds to the PD-L1 gene promoter activating transcription factor-3 (ATF3) to transcriptionally upregulate PD-L1 expression. Our results suggest that it may be an important therapeutic strategy to eradicate intratumoral Fn infection before initiating ESCC immunotherapies.

Date: 2023
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DOI: 10.1038/s41467-023-40987-3

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