TGF-β-miR-34a-CCL22 信号诱导 Treg 细胞募集促进 HBV 阳性肝细胞癌的静脉转移。
TGF-β-miR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma.
机构信息
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
出版信息
Cancer Cell. 2012 Sep 11;22(3):291-303. doi: 10.1016/j.ccr.2012.07.023.
Abstract
Portal vein tumor thrombus (PVTT) is strongly correlated to a poor prognosis for patients with hepatocellular carcinoma (HCC). In this study, we uncovered a causative link between hepatitis B virus (HBV) infection and development of PVTT. Mechanistically, elevated TGF-β activity, associated with the persistent presence of HBV in the liver tissue, suppresses the expression of microRNA-34a, leading to enhanced production of chemokine CCL22, which recruits regulatory T (Treg) cells to facilitate immune escape. These findings strongly suggest that HBV infection and activity of the TGF-β-miR-34a-CCL22 axis serve as potent etiological factors to predispose HCC patients for the development of PVTT, possibly through the creation of an immune-subversive microenvironment to favor colonization of disseminated HCC cells in the portal venous system.
摘要
门静脉癌栓（PVTT）与肝细胞癌（HCC）患者的预后不良密切相关。在这项研究中，我们揭示了乙型肝炎病毒（HBV）感染与 PVTT 发展之间的因果关系。从机制上讲，与 HBV 在肝组织中持续存在相关的 TGF-β 活性抑制了 microRNA-34a 的表达，导致趋化因子 CCL22 的产生增加，从而招募调节性 T（Treg）细胞来促进免疫逃逸。这些发现强烈表明，HBV 感染和 TGF-β-miR-34a-CCL22 轴的活性是促使 HCC 患者发生 PVTT 的重要病因因素，可能是通过创建免疫抑制性微环境来有利于播散性 HCC 细胞在门静脉系统中的定植。
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