肝癌浸润PD1hi CD4+ T细胞的生物学特性、功能及其临床意义研究

Hepatocellular carcinoma (HCC) is one of the most common cancers in China which has posed a great threat on people’s life and health. Immune response plays a critical role in the regulation of the initiation, development and prognosis in HCC, however, a detailed analysis of HCC tumor immune microenvironment is still lacking. In the previous studies, we have performed a systematic study of tumor infiltrating lymphocytes in HCC tumors by using flow cytometry. We have identified a population of CD4+ T cells which highly expressed PD1, which suggests that these cells may play an important role in the development of HCC. Based on this finding, the current proposal is dedicated to perform the following studies: 1) to characterize the phenotypic and molecular features of the PD1hiCD4+ T cells in HCC patients; 2) to investigate the immune regulatory functions of PD1hiCD4+ T cells on both B cell terminal differentiation and CD4+ effector T cell functions; 3) to explore the distribution of PD1hiCD4+ T cells in different stages of HCC and evaluate whether it could be as a prognostic biomarker. Collectively, this research will not only contribute to the understanding of the tumor immune microenvironment in HCC, but also could provide insights for the future immune intervention of this disease.

肝癌是我国最常见恶性肿瘤之一，严重威胁我国人民的生命健康。免疫应答在肝癌发生、发展和预后过程中发挥关键作用，但目前对于肝癌肿瘤免疫微环境缺乏精细的解析。在前期的工作中，我们利用流式细胞术针对肝癌肿瘤浸润淋巴细胞的种类进行了系统分析，发现肝癌肿瘤中存在着一群高表达免疫抑制分子PD1的CD4+ T细胞，提示这群细胞可能在肝癌发生发展过程中发挥了重要作用。在上述工作的基础上，本项目拟开展如下研究：1） 研究肝癌组织PD1hiCD4+ T细胞的表型和分子特征； 2）研究肝癌组织PD1hiCD4+ T细胞对B细胞和效应T细胞的免疫调节作用及其机理；3） 探索PD1hiCD4+ T细胞在肝癌不同发展阶段的分布规律及其预后价值。本研究不但对于阐明肝癌的免疫微环境及其内在调节机制有着重要的意义，而且也可为今后肝癌的免疫治疗提供新的思路。

肝癌是我国最常见恶性肿瘤之一，严重威胁我国人民的生命健康。免疫应答在肝癌发生、发展和预后过程中发挥关键作用，但目前对于肝癌肿瘤免疫微环境缺乏精细的解析。本项目定位于HCC 肿瘤组织中PD1hi CD4+ T 细胞，主要研究内容包括： （1）HCC 肿瘤组织PD1hi CD4+ T 细胞的表型和分子特性；HCC 肿瘤组织PD1hi CD4+ T 细胞的免疫调节机理；PD1hi CD4+ T 细胞的临床意义；（2）发现3个肝脏特异的B细胞亚群；（3）发现肝癌患者浆细胞中IgG编码基因IGHV的组成存在明显偏好。（4）证明PD1hi CD4+ T 细胞以及浆细胞是重要的临床预后指标。综上所述，本研究不但对于阐明肝癌的免疫微环境及其内在调节机制有着重要的意义，而且也可为今后肝癌的诊断以及免疫治疗提供新的思路。