小胶质细胞（MG）在胶质瘤的发展中发挥重要作用，但是具体机制不详。信号转导及转录活化因子3（STAT3）可以抑制小胶质细胞的活性从而促进肿瘤生长。本课题组已证实，晚期糖基化终末产物受体（RAGE）可以作用于STAT3信号通路从而影响小胶质细胞的免疫功能，但是具体调控机制不详。在预实验中，我们发现：高迁移率族蛋白1（HMGB1）在胶质瘤微环境中呈现高表达，并且可以引起小胶质细胞中RAGE的上调。不仅如此，阻断RAGE信号通路后可以部分抑制STAT3的表达。因此，我们推测“HMGB1与RAGE结合后可以上调RAGE的表达，并通过RAGE信号通路进一步激活STAT3信号通路，从而抑制小胶质细胞的免疫活性”是胶质瘤免疫逃逸的新的重要机制。我们拟制备胶质瘤小鼠模型，应用siRNA，活体成像，免疫共沉淀等技术，从组织-细胞-分子层面证明我们的假设，此研究将为胶质瘤的免疫治疗提供新思路和新靶点。

Microglia (MG) have been shown to play an important role in tumorigenesis and glioma development, however the exact mechanism remains unknown. Signal transduction and transcriptional activation factor 3 (STAT3) pathways may promote tumor growth via inhibition the activity of MG. Our previous study has been shown that the immune function of MG could be partially reduced by the receptor of advanced glycosylation end products (RAGE) through the STAT3 pathway, however, the exact mechanism is unclear. Our preliminary data showed that the high mobility group box 1 (HMGB1) was highly expressed in the microenvironment of glioma, which up-regulated RAGE expression of MG in the medium containing HMGB1. In addition, we also observed that the blockage of RAGE pathway may partially repress the activation of STAT3 pathway. We therefore hypothesize that the binding between HMGB1 and RAGE may increase the RAGE expression and thereby the activated RAGE pathway could activate the STAT3 pathway, which in turn inhibit the immune function of MG. This hypothesis may be a mechanism of immune escape of glioma from MG. In the present study, we will prove our hypothesis using intracranial glioma model in mice from tissue-cell-molecule levels by siRNA, living imaging technology, Co-Immunoprecipitation assay and so on. This research will provide a potential target as well as a new method for the immune therapy in glioma.