title: 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, U1015, Equipe labellisée Ligue Nationale Contre le Cancer, Institut Gustave Roussy, Villejuif, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Viaud
authors.forename: Fabiana
authors.initials: F
authors.lastname: Saccheri
authors.forename: Grégoire
authors.initials: G
authors.lastname: Mignot
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamazaki
authors.forename: Romain
authors.initials: R
authors.lastname: Daillère
authors.forename: Dalil
authors.initials: D
authors.lastname: Hannani
authors.forename: David P
authors.initials: DP
authors.lastname: Enot
authors.forename: Christina
authors.initials: C
authors.lastname: Pfirschke
authors.forename: Camilla
authors.initials: C
authors.lastname: Engblom
authors.forename: Mikael J
authors.initials: MJ
authors.lastname: Pittet
authors.forename: Andreas
authors.initials: A
authors.lastname: Schlitzer
authors.forename: Florent
authors.initials: F
authors.lastname: Ginhoux
authors.forename: Lionel
authors.initials: L
authors.lastname: Apetoh
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Chachaty
authors.forename: Paul-Louis
authors.initials: PL
authors.lastname: Woerther
authors.forename: Gérard
authors.initials: G
authors.lastname: Eberl
authors.forename: Marion
authors.initials: M
authors.lastname: Bérard
authors.forename: Chantal
authors.initials: C
authors.lastname: Ecobichon
authors.forename: Dominique
authors.initials: D
authors.lastname: Clermont
authors.forename: Chantal
authors.initials: C
authors.lastname: Bizet
authors.forename: Valérie
authors.initials: V
authors.lastname: Gaboriau-Routhiau
authors.forename: Nadine
authors.initials: N
authors.lastname: Cerf-Bensussan
authors.forename: Paule
authors.initials: P
authors.lastname: Opolon
authors.forename: Nadia
authors.initials: N
authors.lastname: Yessaad
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.forename: Charles O
authors.initials: CO
authors.lastname: Elson
authors.forename: Joël
authors.initials: J
authors.lastname: Doré
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.forename: Patricia
authors.initials: P
authors.lastname: Lepage
authors.forename: Ivo Gomperts
authors.initials: IG
authors.lastname: Boneca
authors.forename: François
authors.initials: F
authors.lastname: Ghiringhelli
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018988:Bacterial Translocation / Q000187:drug effects*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D005856:Germ-Free Life; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000502:physiology; D007156:Immunologic Memory; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007421:Intestine, Small / Q000382:microbiology*; D008221:Lymphoid Tissue / Q000276:immunology / Q000382:microbiology; D051379:Mice; D064307:Microbiota / Q000187:drug effects / Q000502:physiology*; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology / Q000637:transplantation
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide