Regulatory T cells and their associated factors in hepatocellular carcinoma development and therapy

Liver cancer is the third leading cause of cancer-related death worldwide with primary type hepatocellular carcinoma (HCC). Factors, including carcinogens, infection of hepatitis viruses, alcohol abuse, and non-alcoholic fatty liver disease (NAFLD), can induce HCC initiation and promote HCC progression. The prevalence of NAFLD accompanying the increased incidence of obesity and type 2 diabetes becomes the most increasing factor causing HCC worldwide. However, the benefit of current therapeutic options is still limited. Intrahepatic immunity plays critically important roles in HCC initiation, development, and progression. Regulatory T cells (Tregs) and their associated factors such as metabolites and secreting cytokines mediate the immune tolerance of the tumor microenvironment in HCC. Therefore, targeting Tregs and blocking their mediated factors may prevent HCC progression. This review summarizes the functions of Tregs in HCC-inducing factors including alcoholic and NAFLD, liver fibrosis, cirrhosis, and viral infections. Overall, a better understanding of the role of Tregs in the development and progression of HCC provides treatment strategies for liver cancer treatment.