Lee J-K, Seki N, Sayers T J, Subleski J, Gruys E M, Murphy W J, Wiltrout R H
National Genome Research Institute, National Institutes of Health, 5 Nokbun-dong, Eunpyung-ku, Seoul 122-701, Republic of Korea.
Cell Immunol. 2005 Jun;235(2):145-52. doi: 10.1016/j.cellimm.2005.08.029. Epub 2005 Oct 6.
CD40, a member of the TNF receptor superfamily, is expressed on B cells, dendritic cells, and some tumor cells, including melanoma and bladder carcinoma. In this study, we report that both mouse and human renal carcinoma cells (RCC) also constitutively express functional CD40. Treatment of mouse RCC with CD40L induced strong expression of genes and proteins for ICAM-1 and Fas, and this expression was further enhanced by combining CD40L with IFN-gamma. Similar effects were demonstrated using an agonist anti-CD40 antibody. The increased levels of Fas expression on RCC after treatment with CD40L plus IFN-gamma resulted in potent killing by either FasL-positive effector cells or agonistic anti-Fas antibody. The combination of CD40L plus IFN-gamma also significantly enhanced killing of RCC by tumor-specific CTL lines. Our results demonstrate that constitutively expressed CD40 is functionally active and may provide a molecular target for the development of new approaches to the treatment of RCC.
CD40是肿瘤坏死因子受体超家族的一员，在B细胞、树突状细胞以及一些肿瘤细胞（包括黑色素瘤和膀胱癌）上表达。在本研究中，我们报告小鼠和人肾癌细胞（RCC）也组成性表达功能性CD40。用CD40L处理小鼠RCC可诱导ICAM-1和Fas的基因及蛋白强烈表达，并且通过将CD40L与IFN-γ联合使用，这种表达进一步增强。使用激动剂抗CD40抗体也证明了类似的效果。用CD40L加IFN-γ处理后，RCC上Fas表达水平的增加导致FasL阳性效应细胞或激动剂抗Fas抗体的有效杀伤。CD40L加IFN-γ的组合也显著增强了肿瘤特异性CTL系对RCC的杀伤作用。我们的结果表明，组成性表达的CD40具有功能活性，可能为开发治疗RCC的新方法提供分子靶点。
