Emerging Role of PD-1/PD-L1 Inhibitors in Chronic Liver Diseases

Programmed cell death protein 1 (PD-1)/PD-ligand (L)1, the immune checkpoint inhibitors have emerged as a promising strategy for the treatment of various diseases including chronic liver diseases (CLDs) such as hepatitis, liver injury and hepatocellular carcinoma (HCC). The role of PD-1/PD-L1 has been widely inspected in the treatment of viral hepatitis and HCC. PD-1 is known to play a crucial role in inhibiting immunological responses and stimulates self-tolerance by regulating the T-cell activity. Further, it promotes apoptosis of antigen-specific T-cells while preventing apoptosis of T-reg cells. PD-L1 is a trans-membrane protein which is recognized as a co-inhibitory factor of immunological responses. Both, PD-1 and PD-L1 function together to downregulate the proliferation of PD-1 positive cells, suppress the expression of cytokines and stimulate apoptosis. Owing to the importance of PD-1/PD-L1 signaling, this review aims to summarize the potential of PD-1/PD-L1 inhibitors in CLDs along with toxicities associated with them. We have enlisted some of the important roles of PD-1/PD-L1 in CLDs, the clinically approved products and the pipelines of drugs under clinical evaluation.

Automated summary

The PD-1/PD-L1 axis plays a crucial role in inhibiting immune responses and promoting apoptosis, showing promise in the treatment of chronic liver diseases such as hepatitis and liver cancer. Ongoing research aims to explore the potential of PD-1/PD-L1 inhibitors in these conditions and address associated toxicities.