Department of Clinical Therapeutics, Medical School, University of Athens, Alexandra Hospital, 80 Vas. Sofias Avenue, 115 28 Athens, Greece.
Br J Cancer. 2012 Nov 20;107(11):1869-75. doi: 10.1038/bjc.2012.468.
Vascular endothelial growth factor action in tumour angiogenesis is well characterised; nevertheless, it functions as a key element in the promotion of the immune system's evasion by tumours. We sought to investigate the possible direct effect of VEGF on T-cell activation and through which type of VEGF receptor it exerts this effect on cells isolated from ovarian cancer patients' ascites.
T cells isolated from the ascites of ovarian cancer patients were cultured with anti-CD3 and IL-2, with or without VEGF for 14 days and the number of viable T cells was counted. Cytotoxic activity of cultured T cells and expression of VEGF receptor-2 (VEGFR-2), was assayed.
The addition of VEGF in cultures significantly reduced the number and proliferation rate of T cells in a dose-dependent manner and CD3(+) T cells expressed VEGFR-2 on their surface upon activation. Experiments with specific anti-VEGFR-2 antibodies revealed that the direct suppressive effect of VEGF on T-cell proliferation is mediated by VEGFR-2. We also showed that VEGF significantly reduced the cytotoxic activity of T cells.
Our study showed that ascites-derived T cells secrete VEGF and express VEGFR-2 upon activation. Vascular endothelial growth factor directly suppresses T-cell activation via VEGFR-2.
血管内皮生长因子在肿瘤血管生成中的作用已得到充分证实；然而，它也是肿瘤免疫系统逃避的关键因素。我们试图研究 VEGF 对 T 细胞激活的可能直接影响，以及它通过哪种类型的 VEGF 受体对从卵巢癌患者腹水分离的细胞产生这种影响。
用抗 CD3 和 IL-2 培养从卵巢癌患者腹水中分离的 T 细胞，有或没有 VEGF 培养 14 天，并计算活 T 细胞的数量。检测培养的 T 细胞的细胞毒性活性和 VEGF 受体-2（VEGFR-2）的表达。
VEGF 的添加以剂量依赖的方式显著减少 T 细胞的数量和增殖率，并且 CD3(+)T 细胞在激活时在其表面表达 VEGFR-2。用特异性抗 VEGFR-2 抗体进行的实验表明，VEGF 对 T 细胞增殖的直接抑制作用是通过 VEGFR-2 介导的。我们还表明，VEGF 显著降低了 T 细胞的细胞毒性活性。
我们的研究表明，腹水来源的 T 细胞在激活时分泌 VEGF 并表达 VEGFR-2。血管内皮生长因子通过 VEGFR-2 直接抑制 T 细胞激活。
