Chemotherapy-induced ileal crypt apoptosis and the ileal microbiome shape immunosurveillance and prognosis of proximal colon cancer

Roberti MP, Yonekura S, Duong CP, Picard M, Ferrere G, Tidjani Alou M, Rauber C, Iebba V, Lehmann C, Amon L, Dudziak D, Derosa L, Routy B, Flament C, Richard C, Daillère R, Fluckiger A, Van Seuningen I, Chamaillard M, Vincent A, Kourula S, Opolon P, Ly P, Pizzato E, Becharef S, Paillet J, Klein C, Marliot F, Pietrantonio F, Benoist S, Scoazec JY, Dartigues P, Hollebecque A, Malka D, Pagès F, Galon J, Gomperts Boneca I, Lepage P, Ryffel B, Raoult D, Eggermont A, Vanden Berghe T, Ghiringhelli F, Vandenabeele P, Kroemer G, Zitvogel L (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Nature Medicine Nature Publishing Group

DOI: 10.1038/s41591-020-0882-8

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.

Authors with CRIS profile

Christian Lehmann Department of Dermatology Lukas Amon Department of Dermatology Diana Dudziak Professur für die Biologie Dendritischer Zellen

Involved external institutions

École Polytechnique - Université Paris-Saclay FR France (FR) VIB-UGent Center for Inflammation Research BE Belgium (BE) Bicêtre Hospital FR France (FR) Stabilité génétique et oncogenèse FR France (FR) Centre Hospitalier Régional Universitaire de Lille (CHRU de Lille) FR France (FR) Université de Lille (ULille) / University of Lille Nord de France / Université Lille Nord de France / Université Lille II FR France (FR) Centre de Recherche des Cordeliers FR France (FR) University of Orléans / Université d'Orléans FR France (FR) Centre Georges François Leclerc (UNICANCER) FR France (FR) Institut Pasteur FR France (FR) Fondazione IRCCS: Istituto Nazionale dei Tumori IT Italy (IT)

How to cite

APA:

Roberti, M.P., Yonekura, S., Duong, C.P., Picard, M., Ferrere, G., Tidjani Alou, M.,... Zitvogel, L. (2020). Chemotherapy-induced ileal crypt apoptosis and the ileal microbiome shape immunosurveillance and prognosis of proximal colon cancer. Nature Medicine. https://doi.org/10.1038/s41591-020-0882-8

MLA:

Roberti, Maria Paula, et al. "Chemotherapy-induced ileal crypt apoptosis and the ileal microbiome shape immunosurveillance and prognosis of proximal colon cancer." Nature Medicine (2020).

BibTeX: Download