可溶性CD160分子阻遏宫颈癌免疫逃逸的作用及其机制研究

项目名称： 可溶性CD160分子阻遏宫颈癌免疫逃逸的作用及其机制研究

项目编号： No.81201604

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学1

项目作者： 肖晗

作者单位： 华中科技大学

项目金额： 23万元

中文摘要： 肿瘤免疫治疗效果取决于免疫细胞的功能活性。我们以往研究发现肿瘤微环境可高表达某些负性共刺激信号分子诱导T细胞"无能"来实现免疫逃逸，阻断该信号可增强肿瘤特异性T细胞活性。CD160-HVEM是新发现的T细胞活化抑制性信号通路，我们前期研究显示宫颈癌组织和SiHa细胞均高表达CD160和HVEM分子，但其在宫颈癌免疫逃逸中的作用及机制尚不清楚。本项目拟选取宫颈癌为研究对象，从分子、细胞和整体三个水平研究可溶性CD160分子阻遏肿瘤免疫逃逸的作用和机制。通过分析CD160、HVEM分子在病变组织的表达分布及局部浸润T细胞功能活性状况，阐明CD160-HVEM通路在癌变进展过程中诱发的免疫逃逸作用和机制；利用可溶性CD160分子阻断CD160-HVEM信号，在体外混合淋巴细胞培养和免疫重建肿瘤动物模型中验证其逆转T细胞"无能"、阻遏肿瘤免疫逃逸的作用；为建立一种新的肿瘤免疫治疗模式提供依据。

中文关键词： 肿瘤免疫；免疫逃逸；CD160；HVEM；

英文摘要： The therapeutic effect of tumor immunotherapy depends on the activity of tumor antigen specific T cells ultimately. Our past studies have demonstrated the increasing expression of negative regulators of co-stimulatory signals in T lymphocytes in tumor microenvironment, which induces T cell anergy to accept immune escape. The enhancing activity of tumor specific T lymphocytes can be achieved by blocking these signals. CD160-HVEM has been identified as a new inhibitory signal pathway of T cells activation. Although high expression of CD160 and HVEM in cervical cancer tissue and SiHa cells is proved in our primary studies, its underlying functions and mechanisms in immune escape remain unclear. This project plans to investigate the functions and mechanisms of soluble CD160 extracellular segmant molecule to repress cervical cancer immune escape. Here, we describe the pathological expression and distribution of CD160 and HVEM and analyze the function and activity of infiltrating T lymphocytes in tumor tissue. Then, using mixed lymphocytes culture and experimental tumor model of immunological reconstitution SCID mice, we attempt to validate that soluble CD160 may play an important role in the reversal of T lymphocytes anergy and repression of tumor immune escape in vitro and vivo by blocking CD160-HVEM signal pathway.

英文关键词： tumor immunity；immune escape；CD160；HVEM；