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

Yongbin Choi, Jake N. Lichterman, Laura A. Coughlin, Nicole Poulides, Wenling Li, Priscilla Del Valle, Suzette N. Palmer, Shuheng Gan, Jiwoong Kim, Xiaowei Zhan, Yajing Gao, Bret M. Evers, Lora V. Hooper, Chandrashekhar Pasare, Andrew Y. Koh

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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.

Original languageEnglish (US)
Article numbereabo2003
JournalScience Immunology
Volume8
Issue number81
DOIs
StatePublished - Mar 2023

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of 'Immune checkpoint blockade induces gut microbiota translocation that augments extraintestinal antitumor immunity'. Together they form a unique fingerprint.

Cite this