A dendritic cell population generated by a fusion of GM-CSF and IL-21 induces tumor-antigen-specific immunity.
J Immunol
; 185(12): 7358-66, 2010 Dec 15.
Article
en En
| MEDLINE
| ID: mdl-21076067
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 ß(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.
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1
Bases de datos:
MEDLINE
Asunto principal:
Células Dendríticas
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Proteínas Recombinantes de Fusión
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Factor Estimulante de Colonias de Granulocitos y Macrófagos
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Interleucinas
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Linfocitos T CD8-positivos
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Inmunidad Celular
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Neoplasias Mamarias Experimentales
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Melanoma
Límite:
Animals
Idioma:
En
Revista:
J Immunol
Año:
2010
Tipo del documento:
Article
País de afiliación:
Canadá