TIGIT marks exhausted T cells and serves as a target for immune restoration in patients with chronic HBV infection

Background: Chronic HBV infection is a serious worldwide health problem that mainly causes liver cir-rhosis and hepatocellular carcinoma (HCC). Few studies have explored how T cell exhaustion helps HBV avoid immune system attack and how to reverse that exhaustion. Recently, T cell immunoglobulin and immune receptor tyrosine-based inhibitory motif (ITIM) domain (TIGIT) have been identified as coinhibitory receptors, similar to PD-1. This study explores the expression of TIGIT and the T cell function changes in patients with chronic HBV infection. Results: In this study, we found that the expression of TIGIT on T cells increased significantly in patients with chronic HBV infection. High expression of TIGIT on T cells is associated with functional exhaustion. Importantly, this study demonstrates that blocking TIGIT can reverse T cell exhaustion and restore function in patients with chronic HBV infection. Conclusions: HBV induces T cell exhaustion by up-regulating the expression of TIGIT. Blocking the TIGIT/ PVR signaling pathway can reverse T cell exhaustion, so this discovery provides an immunotherapy target to battle chronic HBV infection.