The dual role of regulatory T cells in hepatitis B virus infection and related hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a major contributor to cancer‐related deaths worldwide. Hepatitis B virus (HBV) infection is a major etiologic factor leading to HCC. While there have been significant advancements in controlling HBV replication, achieving a complete cure for HBV‐related HCC (HBV‐HCC) remains an intricate challenge. HBV persistence is attributed to a myriad of mechanisms, encompassing both innate and adaptive immune responses. Regulatory T cells (Tregs) are pivotal in upholding immune tolerance and modulating excessive immune activation. During HBV infection, Tregs mediate specific T cell suppression, thereby contributing to both persistent infection and the mitigation of liver inflammatory responses. Studies have demonstrated an augmented expression of circulating and intrahepatic Tregs in HBV‐HCC, which correlates with impaired CD8⁺ T cell function. Consequently, Tregs play a dual role in the context of HBV infection and the progression of HBV‐HCC. In this comprehensive review, we discuss pertinent studies concerning Tregs in HBV infection, HBV‐related cirrhosis and HCC. Furthermore, we summarize Treg responses to antiviral therapy and provide Treg‐targeted therapies specific to HBV and HCC.