Hepatitis B–Induced IL8 Promotes Hepatocellular Carcinoma Venous Metastasis and Intrahepatic Treg Accumulation

Abstract Hepatitis B–associated hepatocellular carcinoma (HCC) is often accompanied by severe vascular invasion and portal vein tumor thrombus, leading to a poor prognosis. However, the underlying mechanism of this disease remains obscure. In study, we demonstrate that hepatitis B virus (HBV)–encoded gene HBx induces high IL8 production through MEK–ERK signal activation, enhanced endothelial permeability facilitate invasion. metastatic model using tail injection in transgenic mouse with selective expression human CXCR1 endothelium, activation IL8–CXCR1 cascade overexpression cells dramatically liver metastasis. Mechanistically, selectively induced GARP-latent-TGFβ sinusoidal subsequently provoked preferential regulatory T-cell polarization suppress antitumor immunity. Collectively, these findings reveal signaling axis mediates local microenvironmental immune escape HCC induce intrahepatic metastasis, which may serve as potential therapeutic targets for HBV-associated HCC. Significance: This study identifies B–induced IL8/CXCR1/TGFβ suppresses immunity enhances metastasis carcinoma, providing new intervention.