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

Sci Immunol. 2023 Mar 10;8(81):eabo2003. doi: 10.1126/sciimmunol.abo2003. Epub 2023 Mar 3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • CD8-Positive T-Lymphocytes
  • Gastrointestinal Microbiome*
  • Humans
  • Immune Checkpoint Inhibitors
  • Lymph Nodes
  • Melanoma*

Substances

  • Immune Checkpoint Inhibitors