The Intestinal Microbiota Modulates the Anticancer Immune Effects of Cyclophosphamide

Overview

Journal Science

Specialty Science

Date 2013 Nov 23

PMID 24264990

Citations 955

Authors

Sophie Viaud

Fabiana Saccheri

Gregoire Mignot

Takahiro Yamazaki

Romain Daillere

Dalil Hannani

David P Enot

Christina Pfirschke

Camilla Engblom

Mikael J Pittet

Andreas Schlitzer

Florent Ginhoux

Lionel Apetoh

Elisabeth Chachaty

Paul-Louis Woerther

Gerard Eberl

Marion Berard

Chantal Ecobichon

Dominique Clermont

Chantal Bizet

Valerie Gaboriau-Routhiau

Nadine Cerf-Bensussan

Paule Opolon

Nadia Yessaad

Eric Vivier

Bernhard Ryffel

Charles O Elson

Joel Dore

Guido Kroemer

Patricia Lepage

Ivo Gomperts Boneca

Francois Ghiringhelli

Laurence Zitvogel

Affiliations

Soon will be listed here.

Abstract

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.

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