Interleukin-4 plus tumor necrosis factor alpha augments the antigenicity of melanoma cells.
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.
Hoon
D S
DS
John Wayne Cancer Institute, Saint John's Hospital and Health Center, Santa Monica, CA 90404.
Hayashi
Y
Y
Morisaki
T
T
Foshag
L J
LJ
Morton
D L
DL
D015703:Antigens, CD / Q000032:analysis / Q000187:drug effects; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D015139:Blotting, Southern; D002448:Cell Adhesion / Q000187:drug effects; D003601:Cytotoxicity Tests, Immunologic; D004273:DNA, Neoplasm / Q000032:analysis; D004338:Drug Combinations; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006684:HLA-DR Antigens / Q000096:biosynthesis / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D011994:Recombinant Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000494:pharmacology*; D001613:beta 2-Microglobulin / Q000096:biosynthesis / Q000187:drug effects
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D004273:DNA, Neoplasm; D004338:Drug Combinations; D006684:HLA-DR Antigens; D015395:Histocompatibility Antigens Class I; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D001613:beta 2-Microglobulin; D015847:Interleukin-4; D007371:Interferon-gamma