口腔鳞癌中CD24下调M-MDSCs中pVHL促进其向M2-TAM分化的机制研究

口腔鳞癌肿瘤微环境中单核型髓源抑制性细胞（M-MDSCs）通过向M2型肿瘤相关巨噬细胞(M2-TAM)分化进一步抑制抗肿瘤免疫反应。目前这一过程受何种信号调控及其分子机制尚不完全明确。我们前期研究发现口腔鳞癌中M-MDSCs的分化受天然免疫信号CD24的调控，且依赖于介导缺氧诱导因子降解的pVHL。在前期研究基础上，我们提出“口腔鳞癌中CD24通过下调M-MDSCs中pVHL促进其向M2-TAM分化”的科学假说。项目拟从四个方面进行研究：①探究CD24/Siglec-10/pVHL与M-MDSCs、TAM相关性；②CD24促进M-MDSCs向M2-TAM分化的表型及免疫抑制功能研究；③CD24促进M-MDSCs向M2-TAM分化的分子机制研究；④体内探究CD24/pVHL信号对M-MDSCs分化的影响。本研究将为靶向CD24/Siglec-10/pVHL，重塑肿瘤微环境提供策略和理论依据。

Mononuclear myeloid-derived suppressor cells (M-MDSCs) in oral squamous cell carcinoma tumor microenvironment further inhibit anti-tumor immune response through differentiating into M2 like tumor-associated macrophages (M2-TAM). At present, the signal regulation way and molecular mechanism remains not completely clear. Our previous study found that the differentiation of M-MDSCs in oral squamous cell carcinoma is regulated by innate immune signal CD24 and depends on the von Hippel-Lindau protein (pVHL), which mediates the degradation of hypoxia-inducible factor. Thus, we further put forward the scientific hypothesis that CD24 in oral squamous cell carcinoma promotes the differentiation of M-MDSCs to M2-TAM by regulating pVHL in M-MDSCs. This project intends to study from the following four aspects : ①The relationship of CD24/Siglec-10/pVHL and M-MDSCs、TAM; ②The phenotype and immunosuppressive function of CD24 in promoting the differentiation of M-MDSCs to M2-TAM; ③The molecular mechanism of CD24 in promoting the differentiation of M-MDSCs to M2-TAM; ④To explore the effect of CD24/pVHL signaling on M-MDSC differentiation in vivo. This project will provide a therapeutic strategy and theoretical basis for targeting on CD24/Siglec-10/pVHL signals to reshape tumor microenvironment.