肿瘤微环境中，胶质瘤细胞与胶质瘤相关小胶质细胞（GAM）共生存在和相互作用导致胶质瘤免疫抑制，机制仍不明确。我们前期研究证明，miR-340在胶质瘤中发挥重要作用。进一步研究发现，与miR-340表达显著相关的基因主要参与免疫应答，且高表达miR-340可提高GAM细胞吞噬功能。初步研究结果发现，过表达miR-340可抑制胶质瘤细胞细胞因子IL-6家族表达；而IL-6可诱导胶质瘤EZH2表达升高。生物信息学分析显示，EZH2可能通过调控miR-340启动子区的甲基化而抑制其表达。综上，我们提出假设，胶质瘤细胞miR-340表达降低，导致靶基因IL-6家族合成脱抑制，促进GAM细胞转化为促癌型，后者再通过IL-6/EZH2通路阻遏胶质瘤miR-340表达，形成恶性循环导致肿瘤免疫抑制。本项目的研究结果有助于揭示胶质瘤免疫抑制的分子机制，为胶质瘤免疫治疗提供潜在的干预靶点。

The symbiosis and interplay between glioma cells and glioma associated microglia/macrophage (GAM) within the tumor microenvironment leads to tumor immunosuppressant with the mechanisms unelaborated. Our previous work demonstrates that miR-340 plays a vital role in glioma. Further studies show that genes related with miR-340 are found to mainly implicate in immune response, and moreover, overexpression of miR-340 in glioma cells is capable to improve phagocytosis of GAM cells. Our preliminary work shows that overexpression of miR-340 results in inhibition of cytokine IL-6 family in glioma cells, while IL-6 treatment induces up-regulation of miR-340. The analysis of genome locus using UCSC genome browser shows that EZH2 is likely to suppress miR-340 expression through methylation of H3K27 histone within the promoter of miR-340. Collectively, we come up with the hypothesis that down-regulation of miR-340 in glioma contributes to disinhibition of IL-6 family synthesis, resulting in the transformation of GAM cell to the tumor-promoting form; whereas GAM cells in turn blocks miR-340 expression through IL-6/EZH2 pathway in glioma, eventually coming to a vicious circle between glioma and GAM cells promoting the tumor immunosuppression. The expected outcome of this project will help to unravel the molecular mechanism involved in the immunosuppression of glioma, and suggest potential intervention targets of immunal therapies against glioma.