Regulatory T‐cells promote hepatitis B virus infection and hepatocellular carcinoma progression

Abstract Regulatory T‐cells (Tregs), known for their immune suppressive function, have been reported in higher numbers, with activated phenotypes and greater potency, in hepatitis B virus (HBV)‐related liver diseases than in normal conditions. The numbers, phenotypes, and function of intrahepatic and/or tumor‐infiltrating Tregs in HBV‐related liver diseases also differ from those of Tregs in the peripheral blood. By inhibiting the function of effector T‐cells (Teffs), Tregs play a substantial role in the formation and maintenance of the liver's suppressive microenvironment, which might account for the progression of HBV‐related hepatitis and hepatocellular carcinoma (HCC). In acute hepatitis B virus infection, Tregs can safeguard the liver from damage at the cost of prolonged antiviral processes, which results in chronic HBV infection in the liver. Furthermore, Tregs play a role in the development of cirrhosis, the transformation of cirrhosis to HCC, and the progression and metastasis of HCC. Higher levels of Tregs in the peripheral blood and/or tumor sites signify a poorer prognosis in HBV‐related liver conditions, and observational data from mouse models and human patients support the theory that depleting Tregs may be therapeutic in HBV‐related liver diseases by inducing antiviral and antitumor immunity.