Chemoimmunotherapy of tumors: cyclophosphamide synergizes with exosome based vaccines.
Dendritic cell-derived exosomes (DEX) are nanomeric vesicles harboring MHC/peptide complexes capable of promoting primary T cell responses and tumor rejection in the presence of adjuvants. In this study, we show that, in the absence of adjuvants, DEX mediate potent Ag-dependent antitumor effects against preestablished tumors in mice pretreated with immunopotentiating dosing of cyclophosphamide. Cyclophosphamide could 1) abolish the suppressive function of CD4+CD25+Foxp3+ regulatory T cells, 2) markedly enhance the magnitude of secondary but not primary CTL responses induced by DEX vaccines, 3) synergize with DEX in therapy but not prophylaxis tumor models. Therefore, therapeutic vaccines such as DEX aimed at boosting tumor-primed effector T cells could benefit procedures that minimize the effects of CD4+CD25+ regulatory T cells.
ERM-0208 Institut National de la Santé et de la Recherche Médicale, Faculté Kremlin Bicêtre, Institut Gustave Roussy, Villejuif, France.
Julien
J
Taieb
Nathalie
N
Chaput
Noël
N
Schartz
Stéphan
S
Roux
Sophie
S
Novault
Cédric
C
Ménard
François
F
Ghiringhelli
Magali
M
Terme
Antoine F
AF
Carpentier
Guillaume
G
Darrasse-Jèze
Guillaume
G
Darrasse-Jèse
François
F
Lemonnier
Laurence
L
Zitvogel
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002478:Cells, Cultured; D003520:Cyclophosphamide / Q000494:pharmacology*; D022162:Cytoplasmic Vesicles / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000379:methods; D007694:Killer Cells, Natural / Q000276:immunology; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D018906:Antineoplastic Agents, Alkylating; D019496:Cancer Vaccines; D022223:Vaccines, Subunit; D003520:Cyclophosphamide