Immune checkpoint blockade induces gut microbiota translocation that augments extraintestinal anti-tumor immunity
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 summaryFollowing immune checkpoint blockade therapy, dendritic cells traffic gut microbiota into secondary lymphoid organs, promoting optimal extraintestinal anti-cancer immunity.
Kim Jiwoong、Hooper Lora V.、Choi Yongbin、Koh Andrew Y.、Coughlin Laura A.、Poulides Nicole、Gao Yajing、Zhan Xiaowei、Pasare Chandrashekhar
Department of Population and Data Sciences, The University of Texas Southwestern Medical CenterDepartment of Immunology, The University of Texas Southwestern Medical Center||The Howard Hughes Medical Institute, The University of Texas Southwestern Medical CenterDepartment of Pediatrics, Division of Hematology/Oncology, The University of Texas Southwestern Medical Center||Department of Immunology, The University of Texas Southwestern Medical CenterDepartment of Pediatrics, Division of Hematology/Oncology, The University of Texas Southwestern Medical Center||Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center||Department of Microbiology, The University of Texas Southwestern Medical CenterDepartment of Pediatrics, Division of Hematology/Oncology, The University of Texas Southwestern Medical CenterDepartment of Pediatrics, Division of Hematology/Oncology, The University of Texas Southwestern Medical CenterDepartment of Immunology, The University of Texas Southwestern Medical CenterDepartment of Population and Data Sciences, The University of Texas Southwestern Medical CenterDivision of Immunobiology and Center for Inflammation and Tolerance, Cincinnati Children?ˉs Hospital Medical Center Cincinnati||Department of Pediatrics, University of Cincinnati, College of Medicine
肿瘤学基础医学微生物学
Kim Jiwoong,Hooper Lora V.,Choi Yongbin,Koh Andrew Y.,Coughlin Laura A.,Poulides Nicole,Gao Yajing,Zhan Xiaowei,Pasare Chandrashekhar.Immune checkpoint blockade induces gut microbiota translocation that augments extraintestinal anti-tumor immunity[EB/OL].(2025-03-28)[2025-05-16].https://www.biorxiv.org/content/10.1101/2022.01.26.477865.点此复制
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