TGF-beta-miR-34a-CCL22 Signaling-Induced Treg Cell Recruitment Promotes Venous Metastases of HBV-Positive Hepatocellular Carcinoma
Menée sur des échantillons tumoraux prélevés sur des patients atteints d'un carcinome hépatocellulaire associé au virus de l'hépatite B, puis in vitro et in vivo, cette étude met en évidence un mécanisme par lequel, en agissant sur des ceullules immunitaires du micro-environnement tumoral, le facteur TGF-beta favorise le processus métastatique et la formation d'une thrombose portale tumorale
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-² 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-²-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. º HBV positive status predisposes HCC patients to develop PVTT º MiR-34a expression inversely correlates with TGF-² activity and PVTT º HBV-induced TGF-² recruits Treg cells via suppression of miR-34a and induction of CCL22 º TGF-²-miR-34a-CCL22 promotes tumor growth and metastasis via changing microenvironment
Cancer cell , résumé, 2011