PD1

PD1, also known as programmed cell death protein 1 or CD279, is a cell surface receptor that functions as an immune checkpoint in humans. It is encoded by the PDCD1 gene and is primarily expressed on T cells, B cells, and some innate immune cells, with expression upregulated upon activation or chronic antigen exposure.

The PD-1 protein is a type I transmembrane receptor with an immunoglobulin superfamily–like extracellular domain and a cytoplasmic tail containing signaling motifs. Binding of its ligands to PD-1 modulates T cell responses by recruiting phosphatases such as SHP-2, which dampen T cell receptor and co-stimulatory signaling. This leads to reduced proliferation, cytokine production, and cytotoxic activity, contributing to peripheral tolerance and the control of immune responses. PD-1 signaling is also implicated in T cell exhaustion during chronic infections and cancer.

PD-1 engages two ligands: PD-L1 (CD274) and PD-L2 (PDCD1LG2). PD-L1 is widely expressed on hematopoietic and non-hematopoietic cells, including many tumor cells, whereas PD-L2 expression is more restricted to dendritic cells and macrophages. The PD-1/PD-L1 pathway is a central mechanism by which tumors evade immune surveillance, and modulating this axis can restore anti-tumor T cell activity.

Therapeutically, antibodies that block PD-1 or PD-L1 have become standard treatments for multiple cancers, including melanoma, non-small cell lung cancer, renal cell carcinoma, and others. Drugs such as pembrolizumab, nivolumab, cemiplimab, and dostarlimab exemplify this approach. Common immune-related adverse events reflect loss of tolerance and can affect skins, gut, endocrine organs, and other systems.

PD-1 was described in the early 1990s as a regulator of T cell function, shaping modern understanding of immune checkpoints and cancer immunotherapy.