目前，肿瘤微生物组对免疫疗法的影响仍然大部分未知。肿瘤内的妇科宫颈菌（Fn）是一个致癌细菌，能促进食管鳞状细胞癌（ESCC）的肿瘤发展。我们以前的研究发现，Fn是一种早晨的细胞菌，并且它的致病因子Fn-Dps促进了Fn的细胞内存活。在本研究中，我们发现在接受PD-1抑制剂治疗的ESCC患者中，非应答组（NR）中的Fn DNA富集，而Fn的血清抗体水平在非应答组中显著高于应答组（R）。此外，Fn感染对αPD-L1治疗在动物中的疗效有相反的影响。在机理上，我们确认Fn可以抑制T细胞的增殖和细胞因子分泌，并且Fn-Dps能结合到PD-L1基因启动子的转录因子激活因子3（ATF3），以进行转录上调PD-L1表达。我们的结果表明，在开始ESCC免疫疗法之前，根除肿瘤内的Fn感染可能是一种重要的治疗策略。© 2023 Springer Nature Limited.

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.© 2023. Springer Nature Limited.