Suppression of induction and accumulation at tumor site of regulatory T cells by inhibition of VEGF/VEGFR2 pathway

点击翻译按钮获取中文摘要

Regulatory T cells(Treg cells) is one of negative regulators in human immune system. Thus, it is supposed that tumor tissue-infiltrating Treg cells suppress the anti-tumor immunity at the tumor site. If so, suppression of accumulation of Treg cells into the tumor tissue may improve the antitumor immunity. However, only a few therapeutic target molecules for regulating Treg cells are available at present. We showed that vascular endothelial growth factor receptor2(VEGFR2) is a useful therapeutic target against Treg cells. During this research periods, we acquired following new findings.(1) VEGFR2 is selectively expressed on highly-suppressive(FOXP3high) Treg cells.(2) The number of VEGFR2-positive Treg cells is more rich in cancer tissues than in peripheral blood.(3) Chemotactic migration of VEGFR2-positive Treg cells against VEGF is suppressed by addition of an anti-VEGF antibody, Avastin.(4) The number of VEGFR2-positive Treg cells at the tumor site is an independent poor prognostic factor in the colon cancer. These data indicate that VEGFR2-positive Treg cells regulate negatively the antitumor immunity and that VEGF/VEGFR2 pathway may be a useful therapeutic target for improving tumor immunity.