Alterations in gut microbiota impact the pathophysiology of several diseases, including cancer. Radiotherapy (RT), an established curative and palliative cancer treatment, exerts potent immune modulatory effects, inducing tumor-associated antigen (TAA) cross-priming with antitumor CD8+ T cell elicitation and abscopal effects. We tested whether the gut microbiota modulates antitumor immune response following RT distal to the gut. Vancomycin, an antibiotic that acts mainly on gram-positive bacteria and is restricted to the gut, potentiated the RT-induced antitumor immune response and tumor growth inhibition. This synergy was dependent on TAA cross presentation to cytolytic CD8+ T cells and on IFN-γ. Notably, butyrate, a metabolite produced by the vancomycin-depleted gut bacteria, abrogated the vancomycin effect. In conclusion, depletion of vancomycin-sensitive bacteria enhances the antitumor activity of RT, which has important clinical ramifications.

中文翻译：

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肠道微生物群调节树突状细胞抗原呈递和放疗诱导的抗肿瘤免疫反应。

肠道微生物群的改变会影响包括癌症在内的多种疾病的病理生理学。放射疗法 (RT) 是一种既定的治愈性和姑息性癌症治疗方法，具有强大的免疫调节作用，可诱导肿瘤相关抗原 (TAA) 交叉引发与抗肿瘤 CD8+ T 细胞诱导和异位效应。我们测试了肠道微生物群在肠道远端 RT 后是否调节抗肿瘤免疫反应。万古霉素是一种主要作用于革兰氏阳性菌且仅限于肠道的抗生素，它增强了放疗诱导的抗肿瘤免疫反应和肿瘤生长抑制。这种协同作用依赖于 TAA 交叉呈递给溶细胞 CD8+ T 细胞和 IFN-γ。值得注意的是，丁酸盐是一种由万古霉素耗尽的肠道细菌产生的代谢物，它消除了万古霉素的作用。综上所述，