Programmed cell death protein 1 and Programmed cell death 1 ligand 1 interaction (PD-1:PD-L1)

The Programmed cell death protein 1 (PD-1) and Programmed cell death 1 ligand 1 (PD-L1) interaction is a fundamental immune checkpoint pathway that maintains the balance between immune activation and self-tolerance [4, 9]. PD-1 is a receptor primarily expressed on the surface of activated T cells, while its ligand, PD-L1, is expressed on antigen-presenting cells and is frequently overexpressed by various cancer cells to evade immune detection [2, 5, 6]. When PD-L1 binds to PD-1, it triggers inhibitory signaling that suppresses T-cell proliferation, cytokine release, and cytotoxic functions, effectively acting as a "brake" on the immune system [1, 8]. Therapeutic agents targeting this axis, such as monoclonal antibodies, block this interaction to "release the brakes" and reactivate the anti-tumor immune response [3, 13]. This approach has significantly improved outcomes in a wide range of malignancies, including melanoma and non-small cell lung cancer, though it can lead to unique immune-related adverse events due to the loss of self-tolerance [7, 11, 12].

Other names

CD279CD274B7-H1PDCD1PD-1/PD-L1 axisProgrammed death-ligand 1Programmed cell death 1

Monoclonal antibodies block the binding of the PD-L1 ligand to the PD-1 receptor, preventing the transmission of inhibitory signals to T-cells and thereby restoring their anti-tumor activity [1, 3, 8].