肿瘤炎症微环境是影响肝癌发生发展的重要因素。黄嘌呤氧化还原酶XOR能够介导固有免疫和炎症反应，但其在肝癌发生发展中的作用尚不清楚。我们前期研究发现Kupffer细胞表达的XOR参与肝癌发生发展：XOR在人原发性肝癌组织Kupffer细胞中表达明显减低，且其低表达与患者预后不良相关；XOR在M1型巨噬细胞中表达升高，而在M2型巨噬细胞中表达降低；在化学诱导肝癌小鼠Kupffer细胞中XOR的表达显著降低；XOR肝脏条件性敲除小鼠肝脏中Kupffer细胞表型更倾向于M2型巨噬细胞；Kupffer细胞中XOR与STAT1之间存在相互作用，XOR的表达能够抑制JAK-STAT信号通路关键信号分子的磷酸化。本项目拟利用条件敲除基因小鼠、原代巨噬细胞及巨噬细胞系、临床肝癌资料，在动物水平、细胞水平和人体水平，探讨XOR通过调控巨噬细胞极性对肝癌发生发展的影响，以期为肝癌治疗提供新靶点和预后指标。

Tumor environment and inflammation participate in the carcinogenesis and development of hepatocellular carcinoma (HCC). Xanthine oxidoreductase (XOR), mediates immune/inflammatory response. However, the role of XOR in HCC remains unknown. Our previous study indicated that XOR receptor may participate in the tumorigenesis and progression of HCC. XOR expression in Kupffer cells was remarkably reduced in tumor tissues of HCC patients and the low expression of XOR in Kupffer cells of tumor tissues was correlated with poor prognosis. The expression of XOR was increased in M1 macrophage and reduced in M2 macrophage. XOR expression in Kupffer cells was significantly reduced in a chemical-induced HCC mice model. Kupffer cells with XOR deficient was prone to be M2 macrophage. XOR could interact with signal transducer and activator of transcription 1 (STAT1) in Kupffer cells. The expression of XOR could inhibit phosphorylation of critical signal molecules of JAK-STAT signaling pathway. In the present study, we will use liver-specific gene conditional knockout mice, mice primary macrophage and macrophage cell lines, along with clinical liver cancer data to explore the role of XOR in the carcinogenesis and development of HCC via regulating macrophage polarization at animal level, cell level and human level. Our study will provide a new molecular target and a prognostic marker for HCC treatment.