Abstract
Immune cytokines are important regulators of the immune response to neoplastic cells. We previously reported that interleukin 4 (IL-4) and either tumor necrosis factor alpha (TNF) or interferon gamma (IFN) synergistically inhibit melanoma cell growth and induce cell differentiation. In the present study we used various combinations of IL-4, IFN and TNF to enhance the antigenicity of melanoma cells. IL-4 plus TNF significantly increased the ability of melanoma cells to stimulate cytotoxic T cells (CTL) and act as targets of these CTL; IL-4 plus IFN was somewhat less effective, while TNF plus IFN was not as effective. IL-4 plus TNF also increased the expression of HLA class I and HLA-DR antigens on melanoma cells. The CTL lines examined in this study were CD3+CD4+ and oligoclonal. These preclinical results suggest that the immune response to melanoma whole-cell vaccines might be enhanced by pretreating vaccine cells with IL-4 plus TNF.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Antigens, CD / analysis
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Antigens, CD / drug effects
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Antigens, Neoplasm / biosynthesis*
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Blotting, Southern
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Cell Adhesion / drug effects
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Cytotoxicity Tests, Immunologic
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DNA, Neoplasm / analysis
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Drug Combinations
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Gene Rearrangement, beta-Chain T-Cell Antigen Receptor
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HLA-DR Antigens / biosynthesis
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HLA-DR Antigens / drug effects
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Histocompatibility Antigens Class I / biosynthesis
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Histocompatibility Antigens Class I / drug effects
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Humans
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Interferon-gamma / pharmacology
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Interleukin-4 / immunology
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Interleukin-4 / pharmacology*
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Lymphocyte Activation / drug effects
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Lymphocyte Culture Test, Mixed
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Melanoma / drug therapy*
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Melanoma / immunology
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Recombinant Proteins
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T-Lymphocytes, Cytotoxic / drug effects
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T-Lymphocytes, Cytotoxic / immunology
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Tumor Cells, Cultured
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Tumor Necrosis Factor-alpha / immunology
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Tumor Necrosis Factor-alpha / pharmacology*
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beta 2-Microglobulin / biosynthesis
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beta 2-Microglobulin / drug effects
Substances
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Antigens, CD
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Antigens, Neoplasm
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DNA, Neoplasm
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Drug Combinations
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HLA-DR Antigens
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Histocompatibility Antigens Class I
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Receptors, Antigen, T-Cell, alpha-beta
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Recombinant Proteins
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Tumor Necrosis Factor-alpha
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beta 2-Microglobulin
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Interleukin-4
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Interferon-gamma