TGF-β-miR-34a-CCL22 signaling-induced Treg cell recruitment promotes venous metastases of HBV-positive hepatocellular carcinoma.
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.
Yang, P; Li, Q-J; Feng, Y; Zhang, Y; Markowitz, GJ; Ning, S; Deng, Y; Zhao, J; Jiang, S; Yuan, Y; Wang, H-Y; Cheng, S-Q; Xie, D; Wang, X-F
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