Abstract
Granulocyte-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 (betac), 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 betac(-/-) animals developed tumor. Loss of tumor immunity in betac(-/-) 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 betac(-/-) 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 betac(-/-) animals died. Altogether, our results strongly suggest that although endogenous GM-CSF and IL-5 are not required to induce tumor immunity, signaling through betac receptor is critically needed for efficient cancer vaccination in both genetically modified GM-CSF-secreting tumor cells and a spontaneously immunogenic models.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cancer Vaccines / immunology*
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Carcinoma, Renal Cell / immunology
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Carcinoma, Renal Cell / pathology
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Carcinoma, Renal Cell / prevention & control*
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Cell Line, Tumor / metabolism
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Cell Line, Tumor / transplantation
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Culture Media, Conditioned / chemistry
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Cytokine Receptor Common beta Subunit / deficiency
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Cytokine Receptor Common beta Subunit / genetics
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Cytokine Receptor Common beta Subunit / physiology*
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Cytokines / analysis
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Dendritic Cells / immunology
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Dermatitis, Contact / immunology
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Granulocyte-Macrophage Colony-Stimulating Factor / deficiency
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Granulocyte-Macrophage Colony-Stimulating Factor / genetics
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Granulocyte-Macrophage Colony-Stimulating Factor / physiology*
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Injections, Subcutaneous
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Interleukin-3 / deficiency
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Interleukin-3 / genetics
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Interleukin-3 / physiology
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Interleukin-5 / deficiency
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Interleukin-5 / genetics
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Interleukin-5 / physiology
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Kidney Neoplasms / immunology
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Kidney Neoplasms / pathology
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Melanoma, Experimental / immunology
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Melanoma, Experimental / pathology
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Melanoma, Experimental / prevention & control*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Knockout
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Recombinant Fusion Proteins / physiology
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Species Specificity
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Vaccination / methods
Substances
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Cancer Vaccines
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Culture Media, Conditioned
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Cytokine Receptor Common beta Subunit
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Cytokines
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Interleukin-3
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Interleukin-5
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Recombinant Fusion Proteins
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Granulocyte-Macrophage Colony-Stimulating Factor