肝脏浸润PD1+黏膜相关恒定T细胞亚群在合并乙肝感染的肝细胞癌的功能与机制研究

在中国，乙肝病毒（HBV）是引起肝细胞癌(HCC)的主要因素之一。黏膜相关恒定T（MAIT）细胞是肝脏免疫系统的重要细胞亚群。然而，MAIT细胞在乙肝合并肝癌患者中的作用及机制仍不清楚。申请人发现，MAIT细胞在HBV合并HCC患者外周血中数量显著减少并富集于肝脏内；MAIT细胞在患者肝脏中表现为活化衰老状态，其表型为PD1+CD38-CD27+。临床相关性分析提示，富集于肝脏中的MAIT细胞越多，肝损伤程度则越高。我们提出假设：在HCC合并HBV患者中, MAIT细胞通过向肝脏趋化聚集从而在HBV合并HCC的疾病进程起关键作用。本项目拟采用细胞学、生物信息学及肝脏体外模型等方法来解决以下关键科学问题：1）进一步明确MAIT细胞在HCC患者肝脏中的亚群与功能及对疾病进展的调控机制 2）探索MAIT细胞调控肝脏微环境的机制。3）重塑效应性MAIT细胞对HBV合并HCC进展的影响。

In China, hepatitis B virus (HBV) is one of the main causes of HCC. Mucosa associated invariant T (MAIT) cells are important subsets in the liver immunology. However, the role of MAIT cells in patients with HBV combined HCC are still unclear. We found that the number of MAIT cells in the peripheral blood of patients with HBV combined HCC was significantly reduced and enriched in the liver; MAIT cells showed an active but exhaustion phenotype in these patients, and their phenotype was PD1+CD38-CD27+. Clinical correlation analysis showed that the MAIT cells enriched in the liver associated with a higher level of liver injury. We hypothesized that in patients with HBV combined HCC, MAIT cells play a key role in the disease progression of HBV and HCC by chemotaxis to the liver. In this study, cytology, bioinformatics and in vitro liver model are proposed to address the following scientific questions: 1) Clarify the subsets and functions of MAIT cells in the liver of HCC patients and the regulatory mechanism of disease progression; 2) explore the mechanism of MAIT cells regulating liver microenvironment. 3) The effect of remolding effective MAIT cells on the progression of HBV with HCC.