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

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.

SUBMITTER: Li Y

PROVIDER: S-EPMC10507087 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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

Li Yiqiu Y Xing Shan S Chen Fangfang F Li Qifan Q Dou Shuheng S Huang Yuying Y An Jun J Liu Wanli W Zhang Ge G

Nature communications 20230918 1

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 (N ...[more]

PMID: 37723150

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Project description:Esophageal squamous cell carcinoma (ESCC) is a malignant upper digestive tract cancer, and its pathogenesis and etiology are poorly understood. Because gut microbes commonly impact progression, metastasis, and immunotherapy responses in colorectal cancer (CRC), the roles of the esophageal microbiota in ESCC have gradually drawn attention. As reported previously, Fusobacterium nucleatum (Fn), the notable "culprit" of CRC, can also influence the prognosis of ESCC in clinical studies. However, thus far, the underlying mechanism is unclear. In this study, 73 Chinese ESCC samples were collected. In those clinical samples, the abundance of Fn was found to be higher in tumors than in adjacent normal tissues, and a high abundance of Fn was correlated with shorter survival. Furthermore, using in vitro experiments, we demonstrated that Fn can invade ESCC cells, enhancing their proliferation capacity. The mechanism study revealed that Fn can produce high levels of putrescine after invasion, which disturbs polyamine metabolism and promotes the malignant proliferation of ESCC cells. In conclusion, Fn infection was found in Chinese ESCC tumor tissue samples and may promote ESCC progression by disturbing the polyamine metabolism pathway. IMPORTANCE Nowadays, the complex and varied interactions between microbes and human body are known to be crucial for maintaining the health of the human body. However, knowledge concerning the influence of esophageal microbes on the progression of esophageal squamous cell carcinoma is limited. Here, in our study, we confirmed that F. nucleatum can invade ESCC cells and consequently promote their proliferation, suggesting that esophageal microbes likely influence the progression of ESCC in clinical settings. Because the esophagus connects the oral cavity and stomach, acting as a canal for transporting foods, its special physical location makes it easily exposed to microorganisms. Thus, it is necessary to explore the interaction between esophageal microbes and ESCC.

Dataset Information

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

Publications

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

Similar Datasets

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