Abstract
Transduction of B16 melanoma cells with IFN alpha (B16-IFN alpha) enhances CD8(+) T-cell-dependent tumor immunity in mice, resulting in delayed outgrowth in vivo. Here we provide evidence that CD4(+) T cells down-regulate the IFN alpha-induced tumor immune defense. Importantly, depletion of regulatory CD25(+) CD4(+) T cells prevented growth of B16-IFN alpha in most mice and promoted long-lasting protective tumor immunity. Rejection of B16-IFN alpha could also be achieved with therapeutic injections of dendritic cells genetically engineered to express the melanoma antigen tyrosinase-related protein 2. These results support the development of novel strategies for the immunotherapy of melanoma using IFN alpha in combination with elimination of regulatory T cells or antigen-specific immunization.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, Neoplasm / biosynthesis
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Antigens, Neoplasm / genetics
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Antigens, Neoplasm / immunology*
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CD4 Lymphocyte Count
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CD4-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / immunology*
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Cell Division / physiology
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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Dendritic Cells / physiology
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Immunotherapy, Adoptive / methods*
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Interferon-alpha / biosynthesis
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Interferon-alpha / immunology*
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Intramolecular Oxidoreductases / biosynthesis
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Intramolecular Oxidoreductases / genetics
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Intramolecular Oxidoreductases / immunology*
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Melanoma, Experimental / genetics
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Melanoma, Experimental / immunology*
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Melanoma, Experimental / metabolism
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Melanoma, Experimental / therapy
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Mice
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Mice, Inbred C57BL
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Mice, Nude
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Receptors, Interleukin-2 / immunology*
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Receptors, Interleukin-2 / metabolism
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Transduction, Genetic
Substances
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Antigens, Neoplasm
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Interferon-alpha
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Receptors, Interleukin-2
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Intramolecular Oxidoreductases
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dopachrome isomerase