Constitutive expression of functional CD40 on mouse renal cancer cells: Induction of Fas and Fas-mediated killing by CD40L
Constitutive expression of functional CD40 on mouse renal cancer cells: Induction of Fas and Fas-mediated killing by CD40L
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DOI：
10.1016/j.cellimm.2005.08.029
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发表时间：
2005-06-01
影响因子：
4.3
通讯作者：
Wiltrout, RH
中科院分区：
文献类型：
--
作者：
Lee, JK;Seki, N;Wiltrout, RH
CD40 是 TNF 受体超家族的成员，在 B 细胞、树突状细胞和一些肿瘤细胞（包括黑色素瘤和膀胱癌）上表达。在这项研究中，我们报告小鼠和人肾癌细胞 (RCC) 也组成型表达功能性 CD40。用 CD40L 治疗小鼠 RCC 会诱导 ICAM-1 和 Fas 基因和蛋白的强烈表达，并且通过将 CD40L 与 IFN-γ 结合进一步增强这种表达。使用激动剂抗CD40抗体也证明了类似的效果。用 CD40L 加 IFN-γ 治疗后，RCC 上 Fas 表达水平增加，导致 FasL 阳性效应细胞或激动性抗 Fas 抗体产生有效杀伤作用。 CD40L 与 IFN-γ 的组合还显着增强了肿瘤特异性 CTL 系对 RCC 的杀伤作用。我们的结果表明，组成型表达的 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。由爱思唯尔公司出版。
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. Published by Elsevier lnc.