PD-1 and PD-L1 in cancer immunotherapy: clinical implications and future considerations

ABSTRACT

Programmed death-1 (PD-1) is a cell surface receptor that functions as a T cell checkpoint and plays a central role in regulating T cell exhaustion. Binding of PD-1 to its ligand, programmed death-ligand 1 (PD-L1), activates downstream signaling pathways and inhibits T cell activation. Moreover abnormally high PD-L1 expression on tumor cells and antigen-presenting cells in the tumor microenvironment mediates tumor immune escape, and the development of anti-PD-1/PD-L1 antibodies has recently become a hot topic in cancer immunotherapy. Here, we review the structure of PD-1 and PD-L1, the function of the PD-1/PD-L1 signaling pathway, the application of PD-1 or PD-L1 monoclonal antibodies and future directions for anti-PD-1/PD-L1 antibodies with combination therapies. Cancer immunotherapy using PD-1/PD-L1 immune checkpoint blockade may require more studies, and this approach may be curative for patients with many types of cancer in the future.

KEYWORDS:

• PD-1
• PD-L1
• checkpoint
• tumor
• immunotherapy

Disclosure of potential conflicts of interest

The authors have declared that no competing interest exists.

Additional information

Funding

This project was supported by grants from National Natural Science Foundation of China (No. 81671590) and National Basic Research Program of China (973 Program, No. 2014CB541803).