非酒精性脂肪肝双重免疫耐受的特性及其与肝癌的关系

肝癌是致死率第二的恶性肿瘤，至今仍缺乏有效治疗手段。随着经济发展和生活水平、生活习惯的改变，肥胖引起的脂肪肝已成为促进肝癌发生的重要因素。除了肝脏自身的免疫耐受外，肥胖引起的脂肪肝是否以及如何诱导了肝脏的第二重免疫耐受并促进肝癌的发生仍不清楚。我们前期的研究暗示，肥胖引起的脂肪肝会诱导肝脏第二重免疫耐受模式的形成。在本项目中，我们将探索肥胖引起的脂肪性肝病情况下肝脏的区域免疫特性，阐释脂肪性肝病诱导肝脏双重免疫耐受模式并促进肝癌发生发展的细胞分子机制。同时，结合新的纳米药物设计方案，我们也将探究利用纳米药物靶向肝脏双重免疫耐受治疗肝癌的新策略。我们的工作立足于重大疾病，从新的角度阐释脂肪肝中肝脏双重免疫耐受的属性及其与肝癌的关系。研究结果也将为今后治疗脂肪性肝病引发的肝癌提供新策略。

Hepatocellular carcinoma (HCC) is the second cause of cancer death. To date, treatment for advanced HCC is still lacking. Due to the economic development and change of lifestyle, obesity related nonalcoholic fatty liver disease (NAFLD) has been indicated as an important cause of HCC. In addition to the well-known primary immune tolerance in liver, whether and how NAFLD induces secondary immune tolerance and contributes to the growth of HCC remain unclear. Our previous studies imply a secondary immune tolerance pattern related to NAFLD. Here, we will characterize the regional immunity in fatty liver and demonstrate the mechanisms building up dual immune tolerance and contributing to growth of HCC. Additionally, with new nanoparticle delivery system, we will find a new way to target the dual immune tolerance in fatty liver and augment the efficacy of anti-tumor therapies. Our work focuses on major malignant disease and illustrates the pathogenesis via characterizing dual immune tolerance in NAFLD liver and exploring its relationship to HCC. The findings will help to design new therapeutic strategy for NAFLD related HCC.