Role of GM-CSF signaling in cell-based tumor immunization
Copyright policy )Role of GM-CSF signaling in cell-based tumor immunization
AbstractGranulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent adjuvant in cancer vaccination; however, the specific role of endogenous GM-CSF remains unknown. We performed cell-based vaccination in 2 tumor models. First, we vaccinated C57BL/6 mice lacking either GM-CSF, IL-5, or beta-common chain (βc), a receptor subunit essential for GM-CSF and IL-5 signaling, with melanoma cells engineered to produce GM-CSF. Tumor vaccination was effective in both GM-CSF−/− and IL-5−/− mice, showing that protective immunization is independent of both endogenous cytokines. However, all βc−/− animals developed tumor. Loss of tumor immunity in βc−/− mice does not reflect global impairment in cell-mediated immunity, as contact hypersensitivity reaction to haptens is unaltered. The importance of tumor cell–derived GM-CSF was highlighted by recruitment of dendritic cells at the vaccination site in wild-type, GM-CSF−/−, and IL-5−/− but not in βc−/− mice. In the second model, vaccination with unmodified RENCA cells showed similar results with efficient immunization in BALB/c wild-type and GM-CSF−/−, whereas all βc−/− animals died. Altogether, our results strongly suggest that although endogenous GM-CSF and IL-5 are not required to induce tumor immunity, signaling through βc receptor is critically needed for efficient cancer vaccination in both genetically modified GM-CSF–secreting tumor cells and a spontaneously immunogenic models.
- Harvard University United States
- ETH Zurich Switzerland
- French Institute of Health and Medical Research France
- University of Geneva Switzerland
- University Hospital of Geneva Switzerland
Cell Line, Tumor/secretion/transplantation, Melanoma, Experimental, Carcinoma, Renal Cell/immunology/pathology/*prevention & control, Dermatitis, Contact, Interleukin-5/deficiency/genetics/physiology, Cytokine Receptor Common beta Subunit, Kidney Neoplasms/immunology/pathology, Mice, Melanoma, Experimental/immunology/pathology/*prevention & control, Melanoma, Experimental/immunology/pathology/prevention & control, Carcinoma, Renal Cell/immunology/pathology/prevention & control, Granulocyte-Macrophage Colony-Stimulating Factor/deficiency/genetics/physiology, Mice, Knockout, Mice, Inbred BALB C, Recombinant Fusion Proteins/physiology, Kidney Neoplasms, Cytokines, Cytokine Receptor Common beta Subunit/deficiency/genetics/physiology, Granulocyte-Macrophage Colony-Stimulating Factor/deficiency/genetics/*physiology, Culture Media, Conditioned/chemistry, Injections, Subcutaneous, Recombinant Fusion Proteins, Cytokines/analysis, 616.07, Cancer Vaccines, Species Specificity, Cancer Vaccines/immunology, Cell Line, Tumor, 616, 617, Animals, Vaccination/methods, Carcinoma, Renal Cell, Granulocyte-Macrophage Colony-Stimulating Factor, Dendritic Cells, Interleukin-3/deficiency/genetics/physiology, Mice, Inbred C57BL, Dermatitis, Contact/immunology, Cytokine Receptor Common beta Subunit/deficiency/genetics/*physiology, Dendritic Cells/immunology, Culture Media, Conditioned, Interleukin-3, Interleukin-5, Cancer Vaccines/*immunology, ddc: ddc:616.07, ddc: ddc:616, ddc: ddc:617
Cell Line, Tumor/secretion/transplantation, Melanoma, Experimental, Carcinoma, Renal Cell/immunology/pathology/*prevention & control, Dermatitis, Contact, Interleukin-5/deficiency/genetics/physiology, Cytokine Receptor Common beta Subunit, Kidney Neoplasms/immunology/pathology, Mice, Melanoma, Experimental/immunology/pathology/*prevention & control, Melanoma, Experimental/immunology/pathology/prevention & control, Carcinoma, Renal Cell/immunology/pathology/prevention & control, Granulocyte-Macrophage Colony-Stimulating Factor/deficiency/genetics/physiology, Mice, Knockout, Mice, Inbred BALB C, Recombinant Fusion Proteins/physiology, Kidney Neoplasms, Cytokines, Cytokine Receptor Common beta Subunit/deficiency/genetics/physiology, Granulocyte-Macrophage Colony-Stimulating Factor/deficiency/genetics/*physiology, Culture Media, Conditioned/chemistry, Injections, Subcutaneous, Recombinant Fusion Proteins, Cytokines/analysis, 616.07, Cancer Vaccines, Species Specificity, Cancer Vaccines/immunology, Cell Line, Tumor, 616, 617, Animals, Vaccination/methods, Carcinoma, Renal Cell, Granulocyte-Macrophage Colony-Stimulating Factor, Dendritic Cells, Interleukin-3/deficiency/genetics/physiology, Mice, Inbred C57BL, Dermatitis, Contact/immunology, Cytokine Receptor Common beta Subunit/deficiency/genetics/*physiology, Dendritic Cells/immunology, Culture Media, Conditioned, Interleukin-3, Interleukin-5, Cancer Vaccines/*immunology, ddc: ddc:616.07, ddc: ddc:616, ddc: ddc:617
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