ASICs在肿瘤酸化微环境中对MDSCs抑制免疫活性的影响及其机制的研究

项目名称： ASICs在肿瘤酸化微环境中对MDSCs抑制免疫活性的影响及其机制的研究

项目编号： No.81201610

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： 胡鑫

作者单位： 中南民族大学

项目金额： 23万元

中文摘要： 晚期肿瘤患者体内聚集大量髓源抑制细胞(MDSCs)是导致患者免疫功能抑制和肿瘤免疫治疗失败关键因素。肿瘤微环境能够诱导肿瘤MDSCs活化，但启动MDSCs活化的分子机制尚不清楚。申请者前期工作发现MDSCs上表达酸敏感通道（ASICs），H+可以激活ASICs，引起MDSCs出现阳离子内向电流，而且肿瘤微环境MDSCs ASICs表达上调，对H+敏感性增加呈pH依赖性，而ASICs在MDSCs活化过程中的作用国内外尚未见报导。我们推测"ASICs是肿瘤微环境介导MDSCs活化的关键分子"。本课题组将运用电生理学等手段观察在低pH条件下ASICs在MDSCs中的表达规律及其对MDSCs免疫抑制表型的影响及其分子机制。本研究将进一步揭示肿瘤微环境酸化通过ASICs调控MDSCs功能进而影响肿瘤进展转归规律，拓宽MDSCs研究思路，为肿瘤免疫治疗提供新靶标。

中文关键词： 髓样抑制细胞；酸敏感离子通道；活性氧；转化生长因子；

英文摘要： The failure of immunotherapies and antitumor responses contributed to accumulation of MDSCs in patients with advanced stage cancer in vivo. Immunosuppression features of MDSCs could elicit by tumor microenvironment,but the molecular mechanisms have not been fully elucidated. Our previous study demonstrated that extracellular acid can evoke cation inward currents in mice MDSCs via ASICs with pH dependent.The increase of the pH sensitivity in MDSCs with ASICs upregulation was also confirmed.The roles of ASICs play during the process of MDSCs activation have not been reported. So we proposed that ASICs play a key role in MDSCs activation in tumor host.Our term will detect the expression and localization of ASICs in mice MDSCs and its functions in the effect of acidosis on MDSCs immunosuppression phenotype by means of electrophysiology,immunology,cytology,et al.These results may further investigate mechanisms by which acidosis in tumor milieu promote tumor progression through regulation of MDSCs and provide a new target of cancer immunotherapy for future drug design,also as another viewpoint of immunology reseach.

英文关键词： MDSCs；ASICs；ROS；TGF-β1；