肝细胞癌微环境免疫逃逸的分子特征尚不清楚。本项目重点关注H3K27me3组蛋白修饰网络影响肝细胞癌免疫逃逸的具体机制。通过蛋白质谱技术鉴定H3K27me3组蛋白修饰网络介导肝癌免疫逃逸的关键节点分子。构建一系列动物模型阐明TRA2A介导肝细胞癌免疫逃逸及恶性进展的动态网络。利用ChIP-sequenc，RNA-sequence等高通量技术手段阐明TRA2A激活β-catenin通路，富集MDSC介导免疫逃逸的分子机制。设计，优化和评价抑制TRA2A功能的小分子抑制剂。本项目通过研究TRA2A分子改变H3K27me3的再分布状态，激活β-catenin通路，富集MDSC介导肝癌免疫逃逸的机制，阐明组蛋白修饰网络诱导肝癌免疫逃逸的动态过程，为肝癌免疫治疗提供理论依据和药学基础。

The molecular characterization of immune escape microenvironment in hepatocellular carcinoma (HCC) remains unclear. This project focuses on the specific mechanisms of histone modification networks of H3K27me3 in regulation of immune escape in HCC. Identification the key node molecules of H3K27me3 histone modification networks which mediate the immune escape by protein mass spectrometry. Illustration the dynamic network of TRA2A in regulation of the immune escape and malignant progression by constructing a series of animal models. Clarification the molecular mechanisms of TRA2A in activation of the β-catenin pathway which enriches MDSC that mediates immune escape by ChIP-sequence，RNA-sequence and other high-throughput technologies. Design, optimization and evaluation of small molecule inhibitors that inhibit TRA2A function. Through the research of TRA2A in regulation of the redistribution state of H3K27me3 and activation of β-catenin pathway that enriches MDSC mediating immune escape in HCC, this project will clarify the specific mechanism involved in histone modification network that mediates HCC immune escape, and provide theoretical and pharmaceutical basis for HCC immunotherapy.