Immune escape for renal cell carcinoma: CD70 mediates apoptosis in lymphocytes
Immune escape for renal cell carcinoma: CD70 mediates apoptosis in lymphocytes
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DOI：
10.1593/neo.06451
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发表时间：
2006-11-01
期刊：
影响因子：
4.8
通讯作者：
von Eggeling, Ferdinand
中科院分区：
文献类型：
--
作者：
Diegmann, Julia;Junker, Kerstin;von Eggeling, Ferdinand
肿瘤可以通过诱导淋巴细胞凋亡来逃避免疫识别和破坏。尽管肾细胞癌（RCC）能够阻止免疫识别，但迄今为止仅发现了少数与RCC免疫逃逸相关的基因（例如FasL）。我们之前已经证明一些细胞凋亡诱导基因在肾细胞癌中过度表达。我们假设这些基因可能是这些肿瘤免疫逃逸策略的一部分。在此，我们报道 CD70（一种在 RCC 中过度表达的细胞因子）通过与其受体 CD27 和细胞内受体结合蛋白 SIVA 相互作用促进淋巴细胞凋亡。淋巴细胞与RCC细胞系A498和CAKI2共培养后细胞凋亡增加。将重组可溶性 CD70 添加到天然淋巴细胞和 T 细胞系中也会导致淋巴细胞凋亡增加。此外，抗CD27和抗CD70抗体可以部分阻断诱导的细胞凋亡。我们的结果强烈表明 CD70 和 CD27 受体在肿瘤环境中淋巴细胞凋亡中的作用。暴露于肿瘤细胞分泌的 CD70 介导的细胞凋亡可能导致 RCC 患者未能产生有效的淋巴细胞介导的抗肿瘤反应。
Tumors can escape immune recognition and destruction through the induction of apoptosis in lymphocytes. Although renal cell carcinoma (RCC) is able to prevent immune recognition, only a few genes ( such as FasL) that are relevant for RCC immune escape have been identified so far. We have previously shown that some apoptosis-inducing genes are overexpressed in RCC. We hypothesized that these genes could be part of the immune-escape strategy of these tumors. Here we report that CD70, a cytokine overexpressed in RCC, promotes lymphocyte apoptosis through interaction with its receptor CD27 and with the intracellular receptor-binding protein SIVA. Apoptosis increased after cocultivating lymphocytes with the RCC cell lines A498 and CAKI2. The addition of recombinant soluble CD70 to both native lymphocytes and a T-cell cell line resulted in increased lymphocyte apoptosis as well. Furthermore, induced apoptosis could be partially blocked with anti-CD27 and anti-CD70 antibodies. Our results strongly indicate a role for CD70 and CD27 receptor in lymphocyte apoptosis within the tumor environment. Apoptosis mediated by exposure to the CD70 secreted by tumor cells may contribute to the failure of RCC patients to develop an effective lymphocyte-mediated antitumor response.