Gut microbiota, specifically gut bacteria, are critical for effective immune checkpoint blockade therapy (ICT) for cancer. The mechanisms by which gut microbiota augment extraintestinal anticancer immune responses, however, are largely unknown. Here, we find that ICT induces the translocation of specific endogenous gut bacteria into secondary lymphoid organs and subcutaneous melanoma tumors. Mechanistically, ICT induces lymph node remodeling and dendritic cell (DC) activation, which facilitates the translocation of a selective subset of gut bacteria to extraintestinal tissues to promote optimal antitumor T cell responses in both the tumor-draining lymph nodes (TDLNs) and the primary tumor. Antibiotic treatment results in decreased gut microbiota translocation into mesenteric lymph nodes (MLNs) and TDLNs, diminished DC and effector CD8 + T cell responses, and attenuated responses to ICT. Our findings illuminate a key mechanism by which gut microbiota promote extraintestinal anticancer immunity.

中文翻译：

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免疫检查点阻断诱导肠道微生物群易位，增强肠外抗肿瘤免疫力


肠道微生物群，特别是肠道细菌，对于有效的癌症免疫检查点阻断疗法 (ICT) 至关重要。然而，肠道微生物群增强肠外抗癌免疫反应的机制在很大程度上尚不清楚。在这里，我们发现 ICT 诱导特定内源性肠道细菌易位至次级淋巴器官和皮下黑色素瘤。从机制上讲，ICT 诱导淋巴结重塑和树突状细胞 (DC) 激活，从而促进选择性肠道细菌亚群易位至肠外组织，从而促进肿瘤引流淋巴结 (TDLN) 和原发淋巴结中的最佳抗肿瘤 T 细胞反应瘤。抗生素治疗导致肠道微生物群易位至肠系膜淋巴结 (MLN) 和 TDLN 减少，DC 和效应 CD8 减少+ T 细胞反应以及对 ICT 的减弱反应。我们的研究结果阐明了肠道微生物群促进肠外抗癌免疫的关键机制。