title: A dendritic cell population generated by a fusion of GM-CSF and IL-21 induces tumor-antigen-specific immunity.
abstract: We have previously shown that the fusion of GM-CSF and IL-21 (GIFT-21) possesses a potent immune stimulatory effect on myeloid cells. In this study, we define the effect of GIFT-21 on naive murine monocytes (GIFT-21 dendritic cells [DCs]), which express increased levels of Gr-1, CD45R, MHC class I, CD80, CD86, and CXCR4 and suppress CD11c and MHC class II. Compared with conventional dendritic cells, GIFT-21 DCs produced substantially more CCL2, IL-6, TNF-α, and IFN-α and induced significantly greater production of IFN-γ by CD8(+) T cells in MHC class I-restricted Ag presentation assays. B16 melanoma and D2F2 Neu breast cancer growth was inhibited in mice treated with Ag-naive GIFT-21 DCs. This effect was lost in CD8(-/-) and CCR2(-/-) mice and when mice were treated with β(2)-microglobulin-deficient GIFT-21 DCs, indicating that GIFT-21 DCs migrated to and sampled from the tumors to present tumor Ags to CCL2 recruited CD8(+) T cells via MHC class I. We propose that autologous GIFT-21 DCs may serve as a cell therapy platform for the treatment of cancer.
authors.affiliation: Lady Davis Institute, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
authors.forename: Patrick
authors.initials: P
authors.lastname: Williams
authors.forename: Manaf
authors.initials: M
authors.lastname: Bouchentouf
authors.forename: Moutih
authors.initials: M
authors.lastname: Rafei
authors.forename: Raphaëlle
authors.initials: R
authors.lastname: Romieu-Mourez
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hsieh
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Boivin
authors.forename: Shala
authors.initials: S
authors.lastname: Yuan
authors.forename: Kathy Ann
authors.initials: KA
authors.lastname: Forner
authors.forename: Elena
authors.initials: E
authors.lastname: Birman
authors.forename: Jacques
authors.initials: J
authors.lastname: Galipeau
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D000943:Antigens, Differentiation / Q000235:genetics / Q000276:immunology; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D007111:Immunity, Cellular / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D007378:Interleukins / Q000276:immunology*; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D008545:Melanoma / Q000235:genetics / Q000276:immunology* / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D014182:Transplantation, Autologous; D000098546:Interleukin-21
chemical_list: D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D016207:Cytokines; D007378:Interleukins; D011993:Recombinant Fusion Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D000098546:Interleukin-21