法国国家医学研究所（inserm）Laurence Zitvogel研究组近日取得一项新成果。他们发现化疗引起的回肠隐窝凋亡和回肠微生物组可显示免疫监测及预测近端结肠癌（CC）的预后。这一研究成果于2020年5月25日发表在《自然-医学》上。
研究人员发现在CC患者和小鼠中，回肠微生物群决定了回肠小肠上皮细胞（IEC）的耐受性与免疫原性细胞死亡以及滤泡辅助性T（TFH）细胞的积累。抑制小鼠IEC细胞凋亡导致化疗诱导的针对CC的免疫监视受损。针对CC的保护性免疫应答与脆弱拟杆菌 （Bacteroides fragilis）和韦荣球菌（Erysipelotrichaceae）在回肠中的驻留有关。
在存在这些共生菌的情况下，回肠凋亡IEC以白细胞介素-1R1和白细胞介素12依赖的方式诱导产生PD-1 + TFH细胞。回肠微生物组以微卫星不稳定非依赖的方式控制着CC化疗和PD-1阻滞的疗效。这些发现表明免疫原性回肠细胞凋亡有助于化疗治疗CC的预后。
据了解，CC的预后取决于肿瘤浸润性淋巴细胞，包括TFH细胞和化疗诱导的免疫反应的功效。尚不清楚肠道微生物是否有助于诱导TFH细胞驱动的反应。
附：英文原文
Title: Chemotherapy-induced ileal crypt apoptosis and the ileal microbiome shape immunosurveillance and prognosis of proximal colon cancer
Author: Maria Paula Roberti, Satoru Yonekura, Connie P. M. Duong, Marion Picard, Gladys Ferrere, Maryam Tidjani Alou, Conrad Rauber, Valerio Iebba, Christian H. K. Lehmann, Lukas Amon, Diana Dudziak, Lisa Derosa, Bertrand Routy, Caroline Flament, Corentin Richard, Romain Daillre, Aurlie Fluckiger, Isabelle Van Seuningen, Mathias Chamaillard, Audrey Vincent, Stephanie Kourula, Paule Opolon, Pierre Ly, Eugnie Pizzato, Sonia Becharef, Juliette Paillet, Christophe Klein, Florence Marliot, Filippo Pietrantonio, Stphane Benoist, Jean-Yves Scoazec, Peggy Dartigues, Antoine Hollebecque, David Malka, Franck Pags, Jrme Galon, Ivo Gomperts Boneca, Patricia Lepage, Bernard Ryffel, Didier Raoult, Alexander Eggermont, Tom Vanden Berghe, Franois Ghiringhelli, Peter Vandenabeele, Guido Kroemer, Laurence Zitvogel
Issue&Volume: 2020-05-25
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.
DOI: 10.1038/s41591-020-0882-8
Source: https://www.nature.com/articles/s41591-020-0882-8
Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex
本期文章：《自然—医学》：Online/在线发表
