子宫内膜癌源性exosome调控CD39+γδT细胞极化在免疫抑制微环境形成中的作用及机制研究

The development and progression of endometrial cancer is closely related to tumor infiltrating immune cells (TILs). Elucidating the composition of tumor infiltrating immune cells and the key functional subgroups is the most important and difficult point in the effective transformation of endometrial cancer immune microenvironment. However, there are limited studies on TILs in endometrial cancer by far. Our previous studies have shown that endometrial cancer infiltrating CD39+γδT cells are a new subset of immunoregulatory cells, which exert their immunosuppressive function through the adenosine metabolic pathway. This project is intended to study: 1. Phenotypic characteristics and clinicopathological correlation of endometrial cancer infiltrating CD39+γδT cells; 2. Function, position and metabolic mechanism of tumor infiltrating CD39+γδT cells in the formation of endometrial cancer immunosuppressive microenvironment; 3. The mechanisms of chemotaxis and polarization of endometrial cancer infiltrating CD39+γδT cells. Based on the theoretical basis, this project will fully study the clinical significance of endometrial cancer infiltrating CD39+γδT cells, which will help to enhance the understanding of endometrial cancer immune microenvironment, provide new targets and ideas for the treatment of endometrial cancer, and provide experimental basis for the development of new strategies for immunotherapy of endometrial cancer. Thus, this project has important research value and translational significance.

子宫内膜癌的发生发展与肿瘤浸润免疫细胞紧密相关。阐明肿瘤浸润免疫细胞的构成及关键功能亚群是有效改造子宫内膜癌免疫微环境的重点和难点。然而，目前关于子宫内膜癌浸润免疫细胞的研究并不多。我们的前期研究结果显示子宫内膜癌浸润CD39+γδT细胞是一关键免疫调节细胞亚群，通过腺苷代谢通路发挥其免疫抑制功能。本项目拟研究：1、人子宫内膜癌浸润CD39+γδT细胞的表型特征及其临床病理相关性；2、人子宫内膜癌浸润CD39+γδT细胞在免疫抑制微环境形成中的功能、地位及其代谢相关机制；3、人子宫内膜癌浸润CD39+γδT细胞趋化、极化的相关机制。本项目将立足于理论基础，对子宫内膜癌浸润CD39+γδT细胞的临床意义进行充分研究，有助于增进对子宫内膜癌免疫微环境的理解和认识，为子宫内膜癌的治疗提供新的靶点及思路，为开发新的子宫内膜癌免疫治疗策略提供实验依据，具有重要的研究价值及临床转化意义。

子宫内膜癌的发生发展与肿瘤浸润免疫细胞紧密相关。阐明肿瘤浸润免疫细胞的构成及关键功能亚群是有效改造子宫内膜癌免疫微环境的重点和难点。然而，目前关于子宫内膜癌浸润免疫细胞的研究并不多。本项目研究结果显示子宫内膜癌浸润CD39+γδT细胞是一关键免疫调节细胞亚群，通过腺苷代谢通路发挥其免疫抑制功能。子宫内膜癌源性exosome能诱导CD39+γδT细胞极化，进而形成早期子宫内膜癌免疫抑制微环境，进而促进肿瘤进展。本项目对现有结果有助于增进对子宫内膜癌免疫微环境的理解和认识，为子宫内膜癌的治疗提供新的靶点及思路，为开发新的子宫内膜癌免疫治疗策略提供实验依据，具有重要的研究价值及临床转化意义。然而，本项目现阶段结果大部分为体外细胞水平研究，仍需扩大临床样本量进一步验证，并进一步深入研究找出诱导CD39+γδT细胞极化的关键调控分子。