Immune Checkpoint Blockade Induces Gut Microbiota Translocation That Augments Extraintestinal Anti-Tumor Immunity

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 the translocation of specific endogenous gut microbiota 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 which promote optimal anti-tumor T-cell responses in both the tumor-draining lymph nodes (TDLN) and the primary tumor. Antibiotic treatment results in decreased gut microbiota translocation into MLN and TDLN, diminished DC and 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.