PD-1 (PDCD1)

PD-1 (programmed cell death protein 1) is an immune checkpoint receptor that reduces T-cell activity.

Function

PD-1 is expressed on activated T cells, B cells, and myeloid cells. Its ligands - PD-L1 on tumor and stromal cells, PD-L2 on macrophages - bind PD-1 and recruit phosphatases (SHP-2) that dephosphorylate the T-cell receptor’s signaling intermediates. Antigen-stimulated T cells that receive a PD-1 signal reduce cytokine production, proliferation, and cytotoxicity. Physiologically the system limits collateral tissue damage during infection and maintains peripheral tolerance; chronically stimulated T cells in tumors settle into a PD-1-high “exhausted” state.

In cancer

Tumors up-regulate PD-L1 as an immune-evasion mechanism, one of the