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The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide.

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.
AuthorsSophie Viaud, Fabiana Saccheri, Grégoire Mignot, Takahiro Yamazaki, Romain Daillère, Dalil Hannani, David P Enot, Christina Pfirschke, Camilla Engblom, Mikael J Pittet, Andreas Schlitzer, Florent Ginhoux, Lionel Apetoh, Elisabeth Chachaty, Paul-Louis Woerther, Gérard Eberl, Marion Bérard, Chantal Ecobichon, Dominique Clermont, Chantal Bizet, Valérie Gaboriau-Routhiau, Nadine Cerf-Bensussan, Paule Opolon, Nadia Yessaad, Eric Vivier, Bernhard Ryffel, Charles O Elson, Joël Doré, Guido Kroemer, Patricia Lepage, Ivo Gomperts Boneca, François Ghiringhelli, Laurence Zitvogel
JournalScience (New York, N.Y.) (Science) Vol. 342 Issue 6161 Pg. 971-6 (Nov 22 2013) ISSN: 1095-9203 [Electronic] United States
PMID24264990 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Bacterial Agents
  • Antineoplastic Agents
  • Immunosuppressive Agents
  • Cyclophosphamide
Topics
  • Adoptive Transfer
  • Animals
  • Anti-Bacterial Agents (administration & dosage)
  • Antineoplastic Agents (therapeutic use)
  • Bacterial Translocation (drug effects)
  • Cyclophosphamide (therapeutic use)
  • Germ-Free Life
  • Gram-Positive Bacteria (drug effects, physiology)
  • Immunologic Memory
  • Immunosuppressive Agents (therapeutic use)
  • Intestine, Small (microbiology)
  • Lymphoid Tissue (immunology, microbiology)
  • Mice
  • Microbiota (drug effects, physiology)
  • Neoplasms (drug therapy, immunology)
  • Th17 Cells (immunology, transplantation)

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