PUFA重编程MDSC脂质代谢的分子机制及其在肿瘤免疫逃逸中的作用研究

项目名称： PUFA重编程MDSC脂质代谢的分子机制及其在肿瘤免疫逃逸中的作用研究

项目编号： No.81501356

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 鄢德洪

作者单位： 中国科学院深圳先进技术研究院

项目金额： 18万元

中文摘要： 髓系来源的抑制性细胞（MDSCs）抑制抗肿瘤免疫反应，导致肿瘤免疫逃逸发生，这是临床上肿瘤免疫治疗的最大限制因素。我们前期研究表明，多不饱和脂肪酸（PUFAs）影响MDSCs脂质代谢水平，并通过 STAT3 信号通路促进MDSCs的聚集和活化，导致肿瘤免疫逃逸的发生。然而，PUFAs调控MDSCs细胞内脂质代谢的分子机制及其对肿瘤免疫逃逸发生的作用还不清楚。我们又发现，细胞膜上与脂质代谢相关的G蛋白质偶联受体GPR120 和脂质第二信使转运蛋白TIPE3都参与到该过程，这提示PUFAs可能通过 GPR120、TIPE3等脂质代谢通路来引起肿瘤免疫逃逸的发生。据此，本项目拟系统地使用体内外肿瘤模型，围绕MDSCs细胞内GPR120、TIPE3等脂质代谢信号通路展开研究，以期阐明 MDSC脂质代谢异常引起肿瘤免疫逃逸的机制。本项目将对临床上以MDSCs为靶点的肿瘤免疫治疗产生重要的指导意义。

中文关键词： 髓系来源的抑制性细胞；多不饱和脂肪酸；脂质代谢；肿瘤免疫逃逸；免疫抑制

英文摘要： Myeloid-derived suppressor cells (MDSCs) present in most individuals with cancer inhibit antitumor immunity resulting in tumor escape and represent a major limitation in the development of different forms of immunotherapy. In our previous studies, we had confirmed that Polyunsaturated fatty acids (PUFAs) directly changed the lipid metabolism of MDSCs, and then promoted the accumulation and activation of MDSCs by STAT3 signaling pathway resulting in tumor escape. However, the molecular mechanism of PUFAs regulation of lipid metabolism of MDSCs and its effect on tumor escape remained unclear. We recently found that the G protein-coupled receptor GPR120 on the cell membrane and TIPE3, the transfer protein of lipid second messengers,which both of two had some relation with lipid metabolism,were involved in the process.This suggested that PUFAs caused the occurrence of tumor immune escape by GPR120, TIPE3 lipid metabolic pathways . Therefore,basis on these results, this project will systematically use in vivo and in vitro tumor models and intend to focus on studying GPR120 and TIPE3-related signaling pathways in order to clarify the mechanism of tumor escape induced by MDSC's abnormal lipid metabolism. In all, this project will lay a new foundation for the therapeutic potential of targeting MDSC for cancer immunotherapy.

英文关键词： myeloid-derived suppressor cells;Polyunsaturated fatty acids; lipid metabolism ;tumor immune escape;immune suppression