Programmed cell death protein 1 (PD-1)–Programmed death-ligand 1 (PD-L1) axis (PD-1–PD-L1)

The Programmed cell death protein 1 (PD-1)–Programmed death-ligand 1 (PD-L1) axis is a critical immune checkpoint pathway that regulates the balance between immune activation and self-tolerance (Source: UniProt Q15116). PD-1 is an inhibitory receptor primarily expressed on the surface of activated T cells, while its ligand, PD-L1, is often upregulated on tumor cells to evade immune detection (Source: UniProt Q9NZQ7). Under physiological conditions, this interaction prevents overactive immune responses; however, in cancer, it leads to T-cell exhaustion and tumor progression (Source: PubMed PMID: 31510795). Therapeutic targeting of this axis using monoclonal antibodies has revolutionized oncology by restoring the immune system's ability to identify and destroy malignant cells (Source: NIH National Cancer Institute). These drugs, including both PD-1 and PD-L1 inhibitors, are now standard of care for numerous malignancies such as melanoma and non-small cell lung cancer (Source: StatPearls). Despite their success, the systemic activation of T cells can result in immune-related adverse events affecting various organ systems (Source: PubMed PMID: 28942757).

Other names

PD-1/PD-L1 pathwayPDCD1/CD274 axisB7-H1/PD-1 pathwayProgrammed death 1/Programmed death ligand 1 pathway

Monoclonal antibodies bind to either the PD-1 receptor on T cells or the PD-L1 ligand on tumor/immune cells, preventing their interaction. This blockade removes the inhibitory signal that suppresses T-cell activation, thereby restoring the immune system's ability to recognize and eliminate cancer cells (Source: NIH National Cancer Institute).