Crosstalk between TFF2⁺ HCC cells and regulatory T cells drives hepatocellular carcinoma prometastatic niche formation and portal vein tumor thrombosis.

BACKGROUND: Portal vein tumor thrombosis (PVTT) is a critical event that promotes intrahepatic dissemination, induces portal hypertension, and worsens the prognosis of hepatocellular carcinoma (HCC), yet its formation mechanism remains poorly understood. METHODS: HCC cells and the tumor microenvironment, findings that were further corroborated by gene co-expression analysis, cellular co-localization analysis, and immunohistochemistry. Finally, the translational potential of targeting TFF2 was evaluated through in vivo gene knockdown experiments. RESULTS: HCC cells via TGFB1-TGFBR1 interaction, establishing a reciprocal tumor-promoting loop. In vivo models confirmed that TFF2 inhibition suppresses Tregs recruitment and attenuates HCC metastasis. CONCLUSION: HCC cells as a driver of invasive HCC with PVTT, proposing potential therapeutic targets and insights.