Immune Regulation by T Regulatory Cells in Hepatitis B Virus‐Related Inflammation and Cancer

• Published in: Scandinavian journal of immunology Vol. 85; no. 3; pp. 175 - 181
• Main Authors: Trehanpati, N., Vyas, A. K.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.03.2017
• Subjects: Antiviral agents; Carcinoma, Hepatocellular - immunology; Carcinoma, Hepatocellular - pathology; CD4 antigen; CD8 antigen; Cell activation; Chronic infection; Deoxyribonucleic acid; DNA; Hepatitis; Hepatitis B; Hepatitis B virus; Hepatitis B virus - immunology; Hepatitis B, Chronic - immunology; Hepatitis B, Chronic - virology; Hepatocellular carcinoma; Humans; Immune clearance; Immunological tolerance; Immunoregulation; India; Infections; Interferon; Interleukin 10; Interleukin-1 - secretion; Interleukin-10 - secretion; Interleukin-2 - secretion; Liver cancer; Liver Neoplasms - immunology; Liver Neoplasms - pathology; Lymphocytes; Lymphocytes B; Lymphocytes T; Notch protein; PD-1 protein; Programmed Cell Death 1 Receptor - immunology; Signal transduction; T-Lymphocytes, Regulatory - immunology; Transforming Growth Factor beta - secretion; Viral infections; Viral Load - immunology
• ISSN: 0300-9475; 1365-3083; 1365-3083
• DOI: 10.1111/sji.12524

Hepatocellular carcinoma (HCC) is the leading cause of cancer death, and hepatitis B virus (HBV) infection is one of the commonest causes in Asian countries. India has the second largest pool after China for hepatitis B‐infected subjects. HBV clearance is T cell dependent, and one of the reasons for T cells hyporesponsiveness is due to mass production of regulatory T cells (Tregs) through activation of Notch signalling, which suppress CD4/CD8 T cells. Tregs are important to maintain cellular homoeostasis; however, during viral infection increase of Tregs is inversely proportional to HBV DNA titres. Tregs exert their suppressive effect either via cell‐to‐cell contact or through release of interleukin (IL)‐2, IL‐10, TGF‐β and IL‐35. In Chronic hepatitis B virus CHBV infection, PD‐1 pathway also gets activated and is involved in promoting tolerance. However, with Tregs induction, virus‐specific T cell responses also get decreased. Circulatory and intratumoural Tregs promote development of HBV‐specific HCC more by decreasing and impairing the effector functions of CD8 T cells. Antiviral therapies and PD‐1 blockade strategy had shown the inhibition of Tregs and reduction in HBV DNA. However, inhibition of HBV‐specific Tregs is major challenge for future therapies. New cytokine blockade therapies have emerged as potential therapeutic potentials.