The PD-1 (programmed cell death-1) receptor (also known as CD279) is expressed on the surface of activated T cells. Its ligands, PD-L1 (B7-H1; CD274) and PD-L2 (B7-DC; CD273), are commonly expressed on the surface of dendritic cells or macrophages. PD-1 and PD-L1/PD-L2 belong to the family of immune checkpoint proteins that act as co-inhibitory factors, which can halt or limit the development of the T cell response. PD-1/PD-L1 interaction ensures that the immune system is activated only at the appropriate time in order to minimize the possibility of chronic autoimmune inflammation.
Under normal conditions, the immune system performs a series of steps which lead to an anticancer immune response and cancer cell death, known as the cancer immunity cycle1:
1. Tumor cells produce mutated antigens that are captured by dendritic cells
2. The dendritic cells prime T cell with tumor antigen and stimulate the activation of cytotoxic T cells
3. Activated T cells then travel to the tumor and infiltrate the tumor environment
4. The activated T cells recognize and bind to the cancer cells
5. The bound effector T cells
