Immune checkpoint blockade induces gut microbiota translocation that augments extraintestinal antitumor immunity

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. Description Immune checkpoint blockade therapy induces gut bacteria translocation into secondary lymphoid organs and promotes extraintestinal antitumor immunity. Gut microbiota and immune checkpoint blockade Recent studies have suggested that the gut microbiome influences responses to immune checkpoint therapy (ICT) for cancer, but the mechanisms driving these responses are not clear. Choi et al. analyzed the translocation of specific endogenous bacteria from the gut to secondary lymphoid organs or melanoma tumors in a murine model. They observed translocation of some bacterial species during ICT enhanced dendritic cell activation and lymph node remodeling. These enhanced responses promoted antitumor T cell responses in tumor -raining lymph nodes and subcutaneous tumors. In contrast, antibiotic treatment diminished gut microbe translocation to draining lymph nodes and attenuated antitumor responses mediated by ICT. These findings provide critical insight into the role of gut microbe translocation in enhancing the effects of ICT. —CNF