Tim-3介导的CXCR5+CD8+T细胞的功能障碍在HBV相关性肝细胞癌的机制研究

HBV相关性肝细胞癌（HBV-HCC）患者体内存在细胞免疫和体液免疫的双重免疫应答缺陷。课题组前期研究显示，CXCR5+CD8+T细胞在HBV-HCC患者体内发挥细胞免疫和体液免疫双重作用，但调控机制不明。Tim-3可以通过激活PI3K/AKT路径造成效应型T细胞的衰竭。故此推测，HBV-HCC肿瘤细胞可能通过Tim-3激活PI3K/AKT路径从而抑制CXCR5+CD8+T细胞功能，造成细胞免疫和体液免疫的双重障碍，以达到免疫逃避的目的。本课题首先将探讨HBV-HCC患者体内CXCR5+CD8+T细胞的各项功能改变。其次将探讨Tim-3通过PI3K/AKT信号途径对CXCR5+CD8+T细胞功能调控的机制。最后将探讨CXCR5+CD8+T细胞对HBV-HCC临床进程的意义。本课题为明确HBV-HCC的发病机制，开发新型免疫治疗方法打下理论基础。

Patients with HBV-related hepatocellular carcinoma (HBV-HCC) have a double immune response defect in both cellular and humoral immunity. Our previous data showed that CXCR5+CD8+T cells play a dual role in cellular immunity and humoral immunity in patients with HBV-HCC, but the regulatory mechanism is unknown. Tim-3 can cause the exhaustion of effector T cells by activating the PI3K/AKT pathway. Therefore, we speculate that HBV-HCC tumor cells may activate the PI3K/AKT pathway through Tim-3 to inhibit CXCR5+CD8+ T cell function, resulting in a double dysfunction of cellular immunity and humoral immunity, which eventually causes immune evasion. In this study, we will first explore the functional changes of CXCR5+CD8+ T cells in HBV-HCC patients. Then we will examine the mechanism of Tim-3 mediated CXCR5+CD8+ T cell function through PI3K/AKT signaling pathway. Finally, we will investigate the significance of CXCR5+CD8+ T cells in the clinical course of HBV-HCC. This study will provide knowledge for understanding the pathogenesis of HBV-HCC, and help to develop novel immunotherapies for the disease.