Immune checkpoint blockade induces gut microbiota translocation that augments extraintestinal anti-tumor immunity

Abstract Gut microbiota are critical for effective immune checkpoint blockade therapy (ICT) for cancer. The mechanisms by which gut microbiota augment extraintestinal anti-cancer immune responses, however, are largely unknown. Here, we find that ICT induces translocation of specific endogenous gut microbiota into secondary lymphoid organs and subcutaneous melanoma tumors. Mechanistically, gut microbiota activated dendritic cells (DCs) traffic a selective subset of gut bacteria to mesenteric lymph nodes (MLN) and promote optimal anti-tumor T-cell responses in both the tumor draining lymph nodes (TDLN) and the primary tumor. Antibiotic treatment resulted in decreased gut microbiota translocation into MLN and TDLN, diminished polyfunctional effector CD8+ T cell responses, and attenuated response to ICT. Our findings illuminate a key mechanism by which gut microbiota promote extraintestinal anti-cancer immunity. One sentence summary Following immune checkpoint blockade therapy, dendritic cells traffic gut microbiota into secondary lymphoid organs, promoting optimal extraintestinal anti-cancer immunity.