title: Cyclophosphamide induces differentiation of Th17 cells in cancer patients.
abstract: Low doses of the alkylating agent cyclophosphamide (CTX) mediate antiangiogenic and immunostimulatory effects, leading to potent tumoricidal activity in association with various immunotherapeutic strategies. Here, we show in rodents and cancer patients that CTX markedly promotes the differentiation of CD4(+) T helper 17 (Th17) cells that can be recovered in both blood and tumor beds. However, CTX does not convert regulatory T cells into Th17 cells. Because Th17 are potent inducers of tissue inflammation and autoimmunity, these results suggest impact on the clinical management of various types of malignancies treated with alkylating agents and a potential need to optimize CTX-based immunotherapy in patients.
authors.affiliation: Faculté de Médecine de l'Université Paris-Sud XI, Le Kremlin-Bicêtre, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Viaud
authors.forename: Caroline
authors.initials: C
authors.lastname: Flament
authors.forename: Mustapha
authors.initials: M
authors.lastname: Zoubir
authors.forename: Patricia
authors.initials: P
authors.lastname: Pautier
authors.forename: Axel
authors.initials: A
authors.lastname: LeCesne
authors.forename: Vincent
authors.initials: V
authors.lastname: Ribrag
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
authors.forename: Virginie
authors.initials: V
authors.lastname: Marty
authors.forename: Philippe
authors.initials: P
authors.lastname: Vielh
authors.forename: Caroline
authors.initials: C
authors.lastname: Robert
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chaput
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001549:Benzamides; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D007376:Interleukin-2 / Q000008:administration & dosage; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology*; D010879:Piperazines / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D058504:Th17 Cells / Q000187:drug effects* / Q000473:pathology
chemical_list: D018906:Antineoplastic Agents, Alkylating; D001549:Benzamides; D007376:Interleukin-2; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D003520:Cyclophosphamide