Programmed cell death protein 1 (for PD-1) and Programmed cell death 1 ligand 1 (for PD-L1) (PD-1 (for Programmed cell death protein 1), PD-L1 (for Programmed cell death 1 ligand 1))

Programmed cell death protein 1 (PD-1) is a type I transmembrane receptor of the immunoglobulin superfamily, primarily expressed on activated T cells, B cells, and other immune cells. Its major ligand, programmed cell death 1 ligand 1 (PD-L1), is a type I transmembrane glycoprotein from the B7 family, expressed on hematopoietic and many non-hematopoietic cells, including tumor cells. The interaction between PD-1 and PD-L1 serves as a critical immune checkpoint to downregulate immune responses, maintain self-tolerance, and prevent autoimmunity by inhibiting T cell activity upon binding, thus serving as a brake on immune activation. Tumor cells exploit this pathway by upregulating PD-L1, leading to T cell inactivation or exhaustion—this forms the molecular rationale for therapeutic inhibitors of PD-1 or PD-L1, which have become transformative treatments in oncology. The canonical mechanism is that antibody-based drugs targeting PD-1 or PD-L1 block their interaction, thereby restoring T cell activation and anti-tumor cytotoxicity. PD-1/PD-L1 blockade is associated with potent therapeutic effects, particularly in cancers with high expression of PD-L1 or increased neoantigen load, but is also associated with increased autoimmunity and other immune-related toxicities.

Other names

CD279CD274B7-H1

Blockade of PD-1/PD-L1 interaction prevents inhibitory signaling, thereby restoring T-cell function and anti-tumor immunity. Antibodies to PD-1 or PD-L1 bind their targets to block the ligand-receptor signaling, promoting T cell activity against tumor cells.