Hoon D S, Hayashi Y, Morisaki T, Foshag L J, Morton D L
John Wayne Cancer Institute, Saint John's Hospital and Health Center, Santa Monica, CA 90404.
Cancer Immunol Immunother. 1993 Nov;37(6):378-84. doi: 10.1007/BF01526794.
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.
免疫细胞因子是对肿瘤细胞免疫反应的重要调节因子。我们之前报道过白细胞介素4(IL-4)与肿瘤坏死因子α(TNF)或干扰素γ(IFN)协同抑制黑色素瘤细胞生长并诱导细胞分化。在本研究中,我们使用IL-4、IFN和TNF的各种组合来增强黑色素瘤细胞的抗原性。IL-4加TNF显著提高了黑色素瘤细胞刺激细胞毒性T细胞(CTL)的能力,并使其成为这些CTL的靶标;IL-4加IFN的效果稍差,而TNF加IFN则效果不佳。IL-4加TNF还增加了黑色素瘤细胞上HLA I类和HLA-DR抗原的表达。本研究中检测的CTL系为CD3 + CD4 +且是寡克隆的。这些临床前结果表明,用IL-4加TNF预处理疫苗细胞可能会增强对黑色素瘤全细胞疫苗的免疫反应。