The Intestinal Microbiota Modulates the Anticancer Immune Effects of Cyclophosphamide

作者：Sophie Viaud, Fabiana Saccheri, Grégoire Mignot, Takahiro Yamazaki, Romain Daillère, Dalil Hannani, David Pierre Enot, Christina Pfirschke, Camilla Engblom, Mikaël J. Pittet, Andreas Schlitzer, Florent Ginhoux, Lionel Apétoh, Élisabeth Chachaty, Paul‐Louis Woerther, Gérard Eberl, Marion Berard, Chantal Ecobichon, Dominique Clermont, Chantal Bizet, Valérie Gaboriau‐Routhiau, Nadine Cerf–Bensussan, Paule Opolon, Nadia Yessaad, Eric D. Vivier, Bernhard Ryffel, Charles O. Elson, Joël Doré, Guido Kroemer, Patricia Lepage, Ivo Gomperts Boneca, François Ghiringhelli, Laurence Zitvogel · 发表于：Science · 年份：2013 · DOI：10.1126/science.1240537 · 被引用次数：2063 · 研究领域：Gut microbiota and health、Tryptophan and brain disorders、Inflammatory Bowel Disease

Cyclophosphamide is one of several clinically important cancer drugs whose therapeutic efficacy is due in part to their ability to stimulate antitumor immune responses. Studying mouse models, we demonstrate that cyclophosphamide alters the composition of microbiota in the small intestine and induces the translocation of selected species of Gram-positive bacteria into secondary lymphoid organs. There, these bacteria stimulate the generation of a specific subset of "pathogenic" T helper 17 (pT(H)17) cells and memory T(H)1 immune responses. Tumor-bearing mice that were germ-free or that had been treated with antibiotics to kill Gram-positive bacteria showed a reduction in pT(H)17 responses, and their tumors were resistant to cyclophosphamide. Adoptive transfer of pT(H)17 cells partially restored the antitumor efficacy of cyclophosphamide. These results suggest that the gut microbiota help shape the anticancer immune response.