肿瘤发生过程中通常伴随着STAT3的过度活化和NK细胞免疫监视功能的缺陷。近年来，我们的研究发现，阻断肝癌（HCC）细胞中活化的STAT3可以促进HCC的凋亡并抑制其增殖；更重要的是，阻断STAT3可以削弱炎症、打破HCC诱导的NK细胞功能抑制状态，提高机体抗HCC免疫应答。在此基础上，本研究将采用DEN诱导C57BL/6鼠或HBV转基因小鼠建立HCC模型，在动态观察HCC发生发展的过程中，实时监测肝细胞STAT3的活化水平及炎症相关因子的表达水平，同时分析NK细胞表型及功能变化，发现肝细胞中STAT3活化水平与NK细胞功能变化的关系；然后，通过抗体中和、细胞清除/转输等手段，发现肝细胞/HCC内活化的STAT3所调控的下游基因中对NK细胞发挥抑制作用的关键分子或免疫负调细胞。本研究将揭示HCC中STAT3过度活化导致NK细胞功能抑制的细胞与分子机制，为寻找有效治疗肝癌的途径提供新的理论。

In the process of tumor occurrence and development, the excessive activation of STAT3 and impairment of NK cell-mediated immune surveillance are usually observed. Our previous studies have found that blocking STAT3 can promote the apoptosis and inhibit the proliferation of HCC cells; more importantly, blocking STAT3 can weaken the inflammation and break HCC-induced the immunosuppressive stutus of NK cells, as well as improving the host anti-tumor immune response to HCC. Based on these results, during the occurrence and development of HCC in DEN-induced C57BL/6 mice or HBV-tg mice model, we will observe dynamically the inflammation by Immunohistochemical methods. Meanwhile, we will detect instantaneously the activation level of STAT3 in hepatocytes or HCC cells, the profiles of inflammatory cytokines and chemokines,and analyze the phenotype and function of NK cells.Through these works, we will discover the relationship between the activation level of STAT3 in hepatocytes and NK cell function. By means of antibody neutralization, cell deletion/transfer, we will find the key molecules among STAT3 downstream genes or clarify which suppressive immune cells regulate NK cell function. This study will reveal the cellular and molecular mechanisms under which the activated-STAT3 in HCC induce the impairment of NK cell function, and providing new ideas for prevention and treatment of HCC.