胶质瘤微环境中exosome负载的miR-30a介导调节性T细胞活化的机制研究

Immune escape of malignant glioma leads to poor clinical outcome, with regulatory T cells (Treg) playing an important immunosuppressive part in glioma microenvironment. Based on previous finding that glioma can activate Tregs, our group’s further data showed that miR-30a was highly expressed in exosome secreted by glioma cells and upregulated key translational factor STAT5 as well as activation marker Foxp3 in Tregs. Moreover, bioinformatics analysis indicated a negative regulator of STAT5 as the target of miR-30a. Accordingly, we plan to investigate miR-30a mediated activation mechanism of Tregs by glioma as follows. We will clarify exosome-mediated intercellular transportation of miR-30a, explore miR-30a’s regulation of STAT5 through potential target and then examine activation of Tregs by glioma cells with different miR-30a level. Clinical value of relative molecule on diagnosis and prognosis will also be evaluated. In conclusion, our project may reveal a novel mechanism how tumor microenvironment induces glioma’s immune escape, thus providing new targets for future immunotherapy.

恶性胶质瘤逃避机体免疫监视是其临床疗效不佳的关键原因，调节性T细胞（Treg）在胶质瘤微环境中发挥重要的免疫抑制作用。课题组前期工作发现胶质瘤可激活Treg，进一步研究显示：胶质瘤细胞分泌的微囊泡exosome中miR-30a表达水平较高，miR-30a上调Treg关键转录因子STAT5及下游活化标志Foxp3，生物信息学提示miR-30a靶向STAT5的负调控因子。据此，本课题将深入探究胶质瘤通过miR-30a介导的Treg活化机制：在明确胶质瘤源性miR-30a负载于exosome完成细胞间转运的基础上，以Treg为模型解析miR-30a通过潜在靶基因转录调控STAT5的机理，结合体内外实验阐明miR-30a不同状态的胶质瘤细胞对Treg免疫功能的影响，并评估上述通路相关分子应用于胶质瘤诊断及预后的临床价值。预期结果将揭示肿瘤微环境诱导胶质瘤免疫逃逸的新模式，有望为免疫治疗提供新靶点。

恶性胶质瘤逃避机体免疫监视是其临床疗效不佳的关键原因，调节性T细胞(Treg)在胶质瘤微环境中发挥重要的免疫抑制作用。课题组前期工作发现胶质瘤可激活Treg，进一步研究显示:胶质瘤细胞分泌的微囊泡exosome中miR-30a表达水平较高，miR-30a上调Treg关键转录因子STAT5及下游活化标志Foxp3，生物信息学提示miR-30a靶向STAT5的负调控因子。据此，本课题深入探究了胶质瘤通过miR-30a介导的Treg活化机制:在明确胶质瘤源性miR-30a负载于exosome完成细胞间转运的基础上，以Treg为模型解析miR-30a通过潜在靶基因转录调控STAT5的机理，结合体内外实验阐明miR-30a不同状态的胶质瘤细胞对Treg免疫功能的影响，并评估新型免疫治疗方案对Treg的调控机理及疗效。项目结果揭示了肿瘤微环境诱导胶质瘤免疫逃逸的新模式，有望为免疫治疗提供新靶点。