Intratumoral accumulation of gut microbiota facilitates CD47-based immunotherapy via STING signaling

Yaoyao Shi, Wenxin Zheng, Kaiting Yang, Katharine G. Harris, Kaiyuan Ni, Lai Xue, Wenbin Lin, Eugene B. Chang, Ralph R. Weichselbaum, Yang Xin Fu

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Most studies focus on how intestinal microbiota influence cancer immunotherapy through activating gut immunity. However, immunotherapies related to innate responses such as CD47 blockade rely on the rapid immune responses within the tumor microenvironment. Using one defined anaerobic gut microbiota to track whether microbiota interact with host immunity, we observed that Bifidobacterium facilitates local anti-CD47 immunotherapy on tumor tissues through the capacity to accumulate within the tumor microenvironment. Systemic administration of Bifidobacterium leads to its accumulation within the tumor and converts the nonresponder mice into responders to anti-CD47 immunotherapy in a stimulator of interferon genes (STING)- and interferon-dependent fashion. Local delivery of Bifidobacterium potently stimulates STING signaling and increases crosspriming of dendritic cells after anti-CD47 treatment. Our study identifies the mechanism by which gut microbiota preferentially colonize in tumor sites and facilitate immunotherapy via STING signaling.

Original languageEnglish (US)
Article numbere20192282
JournalJournal of Experimental Medicine
Volume217
Issue number5
DOIs
StatePublished - May 4 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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