Programmed cell death protein 1 (PD-1)

Programmed cell death protein 1 (PD-1) is a type I transmembrane immune-inhibitory receptor expressed on T cells, B cells, and NK cells. It interacts with its ligands, PD-L1 and PD-L2, on antigen-presenting or tumor cells to negatively regulate T-cell activation via recruitment of the SHP-2 phosphatase, causing dephosphorylation of key signaling molecules. This results in attenuation of both T cell receptor (TCR) and, primarily, CD28 co-stimulatory signaling, leading to reduced T cell proliferation and cytokine production. The PD-1/CD28 axis is critical for immune homeostasis, allowing peripheral tolerance, but also enables tumor immune evasion when PD-1 is hyperactive. Therapeutic blockade of PD-1 or its ligand (PD-L1) reverses this inhibition, restoring antitumor immune responses and forming the basis for several modern immunotherapies.

Other names

PD1CD279programmed death-1programmed death receptor 1

Most drugs are immune checkpoint inhibitors that block the binding of PD-1 with its ligand PD-L1, preventing recruitment of SHP-2 phosphatase and restoring T cell activation, proliferation, and effector functions. Enhancement of anti-tumor immunity by restoring CD28 co-stimulatory signaling.