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

PD-1 is a type I transmembrane receptor expressed principally on activated T cells, B cells, and macrophages. Its extracellular domain is immunoglobulin-variable (IgV) like, and intracellular tail contains two key signaling motifs (ITIM and ITSM) that transmit negative signals through phosphatase recruitment upon ligand binding. PD-L1, a member of the B7 family, is a type I transmembrane glycoprotein widely expressed on hematopoietic and non-hematopoietic cells, and strongly upregulated on tumor cells in response to inflammatory cues, especially interferon-gamma. Crystal structure studies show a 1:1 binding interface between PD-1 and PD-L1, involving their IgV domains. Their interaction dampens immune activation, inhibits cytokine release and cytotoxicity, and induces T cell exhaustion or apoptosis. Tumors exploit this checkpoint to evade immune destruction. Therapeutic antibodies targeting PD-1 or PD-L1 block this pathway, unleashing anti-tumor immunity and improving survival in many cancers, although with attendant risk of autoimmune reactions.

Other names

PD-1: CD279PD-L1: CD274PD-L1: B7-H1

Blockade of PD-1 or PD-L1 prevents their interaction, thereby inhibiting negative immune signaling. This reverses T cell exhaustion, enhances T cell proliferation, and restores cytotoxicity against tumor cells. IgG monoclonal antibodies are typically used; these can also engage Fc-mediated effector functions such as ADCC and CDC depending on the antibody’s Fc engineering.