| Literature DB >> 32451498 |
Maria Paula Roberti1,2,3, Satoru Yonekura1,2,4, Connie P M Duong1,2, Marion Picard1,2,5, Gladys Ferrere1,2, Maryam Tidjani Alou1,2, Conrad Rauber1,2,4, Valerio Iebba1,2, Christian H K Lehmann6, Lukas Amon6, Diana Dudziak6, Lisa Derosa1,2,3, Bertrand Routy1,2,4, Caroline Flament1,2,3, Corentin Richard7,8, Romain Daillère1,2, Aurélie Fluckiger1,2, Isabelle Van Seuningen9, Mathias Chamaillard10, Audrey Vincent9, Stephanie Kourula11,12, Paule Opolon1, Pierre Ly1,2, Eugénie Pizzato1,2, Sonia Becharef1,2, Juliette Paillet4,13,14, Christophe Klein13, Florence Marliot15,16, Filippo Pietrantonio17,18, Stéphane Benoist19, Jean-Yves Scoazec20, Peggy Dartigues20, Antoine Hollebecque21, David Malka21, Franck Pagès15,16, Jérôme Galon15,16, Ivo Gomperts Boneca5,22, Patricia Lepage23, Bernard Ryffel24, Didier Raoult25, Alexander Eggermont1,2,21, Tom Vanden Berghe11,12, François Ghiringhelli7,8, Peter Vandenabeele11,12,26, Guido Kroemer13,14,27,28,29, Laurence Zitvogel30,31,32,33,34.
Abstract
The prognosis of colon cancer (CC) is dictated by tumor-infiltrating lymphocytes, including follicular helper T (TFH) cells and the efficacy of chemotherapy-induced immune responses. It remains unclear whether gut microbes contribute to the elicitation of TFH cell-driven responses. Here, we show that the ileal microbiota dictates tolerogenic versus immunogenic cell death of ileal intestinal epithelial cells (IECs) and the accumulation of TFH cells in patients with CC and mice. Suppression of IEC apoptosis led to compromised chemotherapy-induced immunosurveillance against CC in mice. Protective immune responses against CC were associated with residence of Bacteroides fragilis and Erysipelotrichaceae in the ileum. In the presence of these commensals, apoptotic ileal IECs elicited PD-1+ TFH cells in an interleukin-1R1- and interleukin-12-dependent manner. The ileal microbiome governed the efficacy of chemotherapy and PD-1 blockade in CC independently of microsatellite instability. These findings demonstrate that immunogenic ileal apoptosis contributes to the prognosis of chemotherapy-treated CC.Entities:
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Year: 2020 PMID： 32451498 DOI： 10.1038/s41591-020-0882-8
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440