摘要
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.
肠道微生物群的改变会影响包括癌症在内的几种疾病的病理生理学。放疗(RT)是一种公认的根治性和姑息性癌症治疗方法，具有很强的免疫调节作用，还有诱导肿瘤相关抗原(TAA)与抗肿瘤CD8+T细胞的交叉诱导及抑癌作用。文章中作者描述了肠道菌群组成对低分割放疗的影响，发现万古霉素治疗对荷瘤小鼠在放疗中引起的抗肿瘤作用有积极影响，并证明改变肠道菌群可以提高放疗效果。万古霉素是一种主要作用于革兰氏阳性细菌且仅限于肠道的抗生素，可增强RT诱导的抗肿瘤免疫反应和抑制肿瘤生长。这种协同作用取决于TAA交叉呈递至溶细胞性CD8 + T细胞和IFN-γ。值得注意的是，万古霉素被耗尽的肠道细菌产生的代谢物丁酸盐消除了万古霉素的作用。总之，对万古霉素敏感细菌的消灭增强了RT的抗肿瘤活性，这具有重要的临床意义。研究结果表明，革兰氏阳性肠道细菌群落的改变可以引起肿瘤微环境重塑，介导引流淋巴结抗原呈递增加，并提高放疗的抗肿瘤作用。由于万古霉素是一种应用广泛且相对安全的临床药物，这些发现提高了利用这种抗生素在增强癌症患者放疗效果的可能性。
文章来源：J Clin Invest. ;130(1):466-479. /10.1172/JCI124332.
