肝癌组织中MHCⅡ#31867;分子的表达与抗肿瘤免疫应答及肝癌术后复发的关系

项目名称： 肝癌组织中MHCⅡ#31867;分子的表达与抗肿瘤免疫应答及肝癌术后复发的关系

项目编号： No.30860324

项目类型： 地区科学基金项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 梅铭惠

作者单位： 桂林医学院

项目金额： 23万元

中文摘要： 肝癌术后复发是患者预后不良的一个重要原因。MHCⅡ#31867;分子是抗原递呈中的关键分子，本项目旨在研究肝癌组织中MHCⅡ#31867;分子影响肝癌患者根治术后复发的机制；以及肿瘤细胞表面MHC- II类分子表达缺失，进而导致肿瘤细胞逃避机体免疫监视的机制。课题组采用免疫组化、流式细胞仪分析、荧光定量PCR和Western blot等技术、方法进行系列研究。结果发现：肝癌组织中MHCⅡ#31867;分子的表达水平与患者术后的无瘤生存时间密切相关，高表达MHCⅡ#31867;分子的肝癌患者容易获得较长术后无瘤生存时间(DFS)；MHCⅡ#31867;分子主要表达在肝癌组织中的淋巴细胞、巨噬细胞和树突状细胞等间质细胞。也就是说，MHCII类分子主要表达在CD68+、CD45RO+和S-100+的细胞上。我们还发现：CD45RO+细胞中的免疫抑制细胞亚群CD4+ CD25+的调节性T细胞（Treg）的抑制功能存在交叉免疫抑制，而且HBV诱导的Treg能够抑制抗肿瘤免疫反应，我们研究显示HBV感染所导致的Treg数量的增多和活化抑制患者发生的针对肝癌的免疫应答，导致肝癌逃避机体免疫监视，对于随后的肝癌发生可能起到重要的促进作用。

中文关键词： 肝细胞癌；MHCⅡ#31867;分子；复发；肿瘤免疫应答

英文摘要： Postoperative tumor recurrence is the major cause for poor prognosis in patient with hepatocellular carcinoma(HCC). MHC II molecules play an important role in the antigen presenting process. In this study we investigate:1)the mechanism of MHC II molecules in tumor tissue influecing on tumor recurrence postoperatively;2)the mechanism of lack expression of MHC II on the tumor cell surface resulting in an immune escape of the cells from the body. The following techniques,including immunohistochemistry, flow cytometry, real time PCR and western blot analysis etc. were applied to this study. Our study demonstrated that the expression level of MHC II molecules is closely related to the disease free survival (DFS) of HCC patients underwent surgical resection: patients who had a high expression level of CIITA and MHCII molecules, had a better DFS. The molecule expressions mostly were in lymphcyte,macrophagocyte and dentritic cell of the tumor tissue .In other words, the expression of MHCII molecules were found to be located in CD68+ cells, CD45RO+ cells and S-100+ cells. We also found that CD45RO+ cell containing CD4+CD25+ regulatory T cells which play cross immune inhibit functions. Regulatory T cell (Treg) induced by HBV infection can inhibit the anti-tumor immnue response, which lead to immune escape of HCC and subsequently may promote the carcinogenesis of the disease.

英文关键词： hepatocellular carcinoma; MHC II molecule; recurrence; anti-tumor immune response