TGF-β通过lncRNA介导肝细胞癌浸润性淋巴细胞功能抑制的机制研究

Tumor microenvironment played an important role in cancer progression, the immune system plays a dual role in cancer: it can not only suppress tumor growth and invasion but also promote caner progression either by immunoselection or establishing an immune inhibition network within the tumor microenvironment that facilitate cancer development. The role of long noncoding RNA (lncRNA) in cancer cell dissemination is well established, but the involvement of lncRNAs in immune cells is still unknown. In this study, we assume that TGF-β impaired functions of intratumoral T cells in hepatocellular carcinoma through lncRNA. In order to study lncRNA expressed in the sorted populations from different locations (peritumoral microenviroment and intratumoral microenvironment) of hepatocellular carcinoma (HCC) patients, a lncProfiler lncRNA qPCR array was performed. After validation, PCR analysis was done to asses the association with prognosis of HCC patients. Using purified T cells from peritumoral and intratumoral tissues, in vitro functional assay was conducted to assess whether upregulated and downregulated lncRNA in immune cells had the effect on the tumor cells. These results may indicate a new TGF-β mediated mechanism by which tumor microenvironment could influence immune cells.

免疫微环境与肿瘤细胞相互作用导致肿瘤细胞死亡或者形成免疫抑制网络，使局部效应细胞功能减弱或“失能”，实现免疫逃逸。TGF-β及IL-10是肿瘤局部典型的免疫抑制分子，通过诱导抑制性免疫细胞浸润、改变局部细胞因子环境、抑制效应细胞功能从而促进肿瘤进展。TGF-β活化的长链非编码RNA促进肝癌的侵袭转移。既往的研究多集中在肝癌细胞上，而长链非编码RNA在免疫细胞亚群中亦有明显的表达差异。我们设想，TGF-β通过lncRNA介导肝癌浸润性淋巴细胞功能抑制。本课题通过lncRNA芯片对肝癌组织及癌旁组织浸润淋巴细胞进行lncRNA表达谱分析，通过生物信息学的方法筛选出具有表达差异的lncRNA，并验证筛选兴趣lncRNA，通过分析高通量组织芯片的结果进行统计与预后和转移复发的关系，应用转染或者过表达进行lncRNA对肝癌浸润淋巴细胞的功能研究，阐明肝癌局部免疫抑制分子与浸润淋巴细胞作用的内在机制。