免疫治疗已成为恶性肿瘤临床治疗的新方向，但对于肿瘤免疫微环境的调控机制尚未阐明。本课题组前期研究发现黄嘌呤氧化还原酶（XOR）表达与肝癌微环境中免疫细胞浸润相关，进一步研究表明肿瘤相关巨噬细胞（TAM）中XOR表达可介导其表型极化，从而调控免疫细胞的抗肿瘤效应。通过基因芯片和质谱技术分析确定了XOR结合TRIM21蛋白调控TLR2表达和活化从而介导了巨噬细胞的极化过程。本研究拟采用基因突变体构建，免疫共沉淀技术对XOR-TRIM21蛋白结合具体位点进行验证。通过细胞和动物模型，借助分子生物学技术深入探讨XOR/TRIM21/TLR2调节轴在肝癌免疫微环境调控中的作用方式和分子机制，解析下游效应途径及靶点。同时，从大样本回顾性分析中总结TAM中XOR表达对于肝癌患者的临床相关性和预后判断价值，以期为肝癌免疫治疗提供新的靶点及理论依据。

The regulatory mechanism of immunotherapy on tumor immune microenvironment has not been elucidated, even though it is a new direction for clinical treatment of malignant tumors. Previous studies have found that the expression of xanthine oxidoreductase (XOR) is related to immune cell infiltration in the microenvironment of hepatocellular carcinoma. Further research indicates that overexpression of XOR in tumor-associated macrophages (TAM) can mediate the phenotypic polarization, and then regulate the anti-tumor effect of immune cells. Our team determined that XOR combined with TRIM21 protein regulates TLR2 expression and activation so as to mediate the polarization process of macrophages by gene chip and mass spectrometry analysis. This study intends to verify the specific binding site of XOR-TRIM21 protein by using gene mutant construction and co-immunoprecipitation technology. We deeply explore the molecular mechanism of XOR / TRIM21 / TLR2 signaling axis in the immune microenvironment of hepatocellular carcinoma, and analyze the downstream pathways and targets through molecular biology techniques in vivo and vitro. Meantime, we intend to summarize the clinical relevance and prognostic value of XOR expression in TAM for HCC patients by retrospective analysis of a large sample. Taken together, we hope to provide new targets and theoretical basis for hepatocellular carcinoma immunotherapy.