TLR8对肝癌细胞的免疫调控及其靶向治疗

项目名称： TLR8对肝癌细胞的免疫调控及其靶向治疗

项目编号： No.81502063

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 周志侠

作者单位： 青岛大学

项目金额： 18万元

中文摘要： TLR8是Toll样受体家族主要成员之一，在机体固有免疫和获得性免疫反应中发挥重要作用。TLR8不仅表达于多种免疫细胞，也表达于肿瘤细胞，但其对肿瘤细胞的确切作用及调控机制尚不清楚。本项目拟以人肝癌细胞为研究对象，以TLR8信号通路的活化/抑制为手段，通过对原发性肝癌组织和肝癌细胞系TLR8的表达、功能及其与细胞周期/凋亡相关分子、NKG2D配体和MicroRNAs 相互调控关系的探讨，阐明TLR8对肝癌细胞作用分子调控机制；并进一步通过稳定表达荧光的肝癌细胞系，或临床肝癌组织建立裸鼠肝癌模型，明确TLR8激动剂或拮抗剂的直接抗瘤作用或免疫佐剂效应。研究结果将加深我们对TLR8免疫调控功能的了解，同时为新型抗肿瘤药物或疫苗佐剂的研发开拓思路。

中文关键词： TLR8；肝细胞癌；免疫调控；免疫治疗

英文摘要： TLR8 is one of the key members of Toll-like receptor (TLR) family, it plays an important role in host innate immune and acquired immune responses. TLR8 is not only expressed in a variety of immune cells, but also expressed in tumor cells. However, the function and regulatory mechanisms of TLR8 in tumor cells remains unknown. In this project, we intend to observe the expression and function of TLR8 in human clinical primary liver cancer tissue and hepatocellular carcinoma cell lines stumulated with TLR8 agonists and antagonists. In further, to investigate the mechanisms of TLR8 effects on hepatocellular carcinoma cells, we will examined the regulation roles of the immune regulatory factors in these cells, including the cell proliferation/apoptosis-related molecules, the NKG2D ligands, and MicroRNAs (miRNAs) via siRNAs, inhibitors, or protein blocking agents. These results will reveal the exact roles and mechanism of TLR8 in hepatocellular carcinoma cells. In addition, in order to clarify the direct anti-tumor effects or immune adjuvant effects of TLR8 agonist or antagonist on human hepatocellular carcinoma，liver cancer models in nude mice will be established by hepatocellular carcinoma cell line maintained stable fluorescence expression, or by small pieces of primary liver cancer tissues. The data of this project will deepen our understanding of the immune regulation of TLR8 in human, as well as provide insights to the development of new anticancer drugs or vaccine adjuvant.

英文关键词： TLR8;HCC;immune regulation;immunotherapy