Immune checkpoints on T and NK cells in the context of HBV infection: Landscape, pathophysiology and therapeutic exploitation

In hepatitis B virus (HBV) infection, the interplay between the virus and the host immune system is crucial in determining the pathogenesis of the disease. Patients who fail to mount a sufficient and sustained anti-viral immune response develop chronic hepatitis B (CHB). T cells and natural killer (NK) cells play decisive role in viral clearance, but they are defective in chronic HBV infection. The activation of immune cells is tightly controlled by a combination of activating and inhibitory receptors, called immune checkpoints (ICs), allowing the maintenance of immune homeostasis. Chronic exposure to viral antigens and the subsequent dysregulation of ICs actively contribute to the exhaustion of effector cells and viral persistence. The present review aims to summarize the function of various ICs and their expression in T lymphocytes and NK cells in the course of HBV infection as well as the use of immunotherapeutic strategies targeting ICs in chronic HBV infection.

Automated summary

In HBV infection, the interaction between the virus and the host immune system determines the development of the disease. Failure to mount a sufficient anti-viral immune response leads to chronic HBV infection. T cells and NK cells are crucial for viral clearance but are defective in chronic HBV infection. The dysregulation of immune checkpoints contributes to immune exhaustion and viral persistence. This review summarizes the expression and function of immune checkpoints in T and NK cells during HBV infection and discusses immunotherapeutic strategies targeting immune checkpoints in chronic HBV infection.