Toll样受体在激活固有免疫，触发适应性免疫应答中发挥重要作用。已知脑内特有的固有免疫细胞——小胶质细胞在脑胶质瘤局部聚集，但发挥免疫抑制活性，促进负性免疫微环境形成，改善或逆转小胶质细胞的抑制性功能至关重要。我们前期研究发现，小胶质细胞表达TLR1/2受体，TLR1/2激动剂BLP通过诱导小胶质细胞活化，促其分泌多种正性细胞因子和趋化因子，不但逆转其抑制功能，而且促进T细胞的增殖及迁移，提高肿瘤局部效应T细胞的数量。基于此，本研究拟以原位脑胶质瘤荷瘤小鼠为模型，聚焦小胶质细胞，利用免疫学、影像学和分子生物学等方法，体内、外研究TLR1/2信号对小胶质细胞免疫学特征及功能的影响；进一步分析TLR1/2信号依赖的小胶质细胞对免疫微环境和T细胞抗肿瘤免疫应答的效应及其机制。该项研究将为TLR信号作用于小胶质细胞改善或逆转脑内固有和适应性免疫应答提供新的理论和实验依据。

Toll-like receptors play a role in the induction of innate immunity, which further triggers adaptive immunity. Microglia, the only resident immune cells in brain, accumulate at the tumor site to induce suppressive activity, and consequently form the immunosuppressive glioma microenvironment. Therefore, the key for the effective anti-glioma immunotherapy might be to improve or even reverse the immunosuppression. In our previous study, we found that microglia expresses TLR1/2. And microglia activated by TLR1/2 agonist secreted multiple positive cytokines and chemokines. These cytokines/chemokines reversed the immunosuppression of microglia to enhance T cell proliferation, migration and also increase effector T cell number at the tumor site. Based on the above background, in this study, glioma-bearing mice are as a model, microglia in brain are as objects, and immunology, iconography and molecular biology are as methods. Under TLR1/2 signal, the phenotype and functional characteristics of microglia will be investigated and also confirmed in chimeric mice, TLR2-/- mice and CX3CR1CreER mice models. Furthermore, the effects of TLR1/2-dependent microglia on tumor immune microenvironment and T cell-mediated anti-tumor immunity will be explored. Thus, this study will supply new theories and basis for TLR1/2-dependent microglia to make innate and adaptive immunity better in glioma microenvironment.