Abstract
Achieving a functional cure for chronic hepatitis B virus (HBV) infection or complete elimination of HBV covalently closed circular DNA (cccDNA) has been challenging in the treatment of patients with chronic HBV infection. Although novel antivirals are being investigated, improving HBV-specific adaptive immune responses is also important for durable viral clearance. Tissue-resident memory CD8+ T (TRM) cells were recently reported as a T-cell population that resides in peripheral tissues and does not recirculate. TRM cells have been studied in the livers of mice and humans. Liver TRM cells have distinct characteristics compared to T cells in peripheral blood or other tissues, which may be associated with the unique microenvironment of the liver. In this review, we describe the characteristics of liver TRM cells and their implications in chronic HBV infection. We emphasize that liver TRM cells can be an immunotherapeutic target for the treatment of chronic HBV infection.
Highlights
Hepatitis B virus (HBV) is a major risk factor for liver cirrhosis (LC) and hepatocellular carcinoma (HCC)
We found that hypoxia-induced factor-2α (HIF-2α) was upregulated in the CD103− subpopulation compared to the CD103+ subpopulation, and its expression was associated with the function and survival of the CD103− subpopulation [46]
nucleoside analogue (NUC) treatment, closed circular DNA (cccDNA) persists in infected hepatocytes
Summary
Hepatitis B virus (HBV) is a major risk factor for liver cirrhosis (LC) and hepatocellular carcinoma (HCC). HBVspecific immune responses are insufficient for elimination of the virus in chronic HBV infection [3]. CD8+ cytotoxic T cells are one of the major players in the adaptive immune system, which recognizes viral epitopes loaded on major histocompatibility complex (MHC) class I molecules, thereby eliminating viruses by killing virus-infected cells or releasing antiviral cytokines [5]. In ex vivo experiments, blocking inhibitory receptors had only partial effects on the restoration of HBV-specific T-cell [6] and B-cell [7] responses. A recent pilot human trial showed that blocking programmed cell death-1 (PD-1) had a partial effect in decreasing the level of HBV surface antigen (HBsAg) [8]. We describe recent studies of liver TRM cells and discuss whether they could be potential therapeutic targets for the treatment of chronic
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