Programmed death-1 (PD-1), also known as CD279, is another important negative costimulatory molecule. It is a protein in humans that is encoded by PDCD1 gene.

Ligands of PD-1

The ligands of PD-1 include: PD-L1 (B7-H1, CD274) and PD-L2 (B7-H2, CD273). The affinity between PD-L2 and PD-1 is 2-6 times that of PD-L1, but PD-L1 is the main ligand of PD-1, which is highly expressed in various malignant tumors. Both ligands are located on the human chromosome 9p24 and share similar extracellular domains. The homology of PD-L1 and PD-L2 is 40%.

PD-1 and its ligands belong to the CD28/B7 superfamily.

PD-L1/PD-1 Signaling Pathway

PD-1 binds with its main ligand PD-L1 to form the PD-1/PD-L1 signaling pathway. The process of the pathway is as follows: After PD-1 binds to its ligand PD-L1, tyrosine in the ITSM domain of PD-1 cytoplasmic region is phosphorylated, and SHP2 phosphatase molecules are recruited to cell membrane. These phosphatases dephosphorylate TCR receptor-associated signaling molecules ZAP70, PKCθ, and CD3ζ near the membrane, thereby inhibiting TCR/CD28 signaling. PD-1 signaling also inhibits CD28 - mediated PI3K activation, thereby reducing Akt phosphorylation and glucose metabolism.

The Function of PD-L1/PD-1 Signaling Pathway

PD-L1/PD-1 signaling pathway regulates T cell activation and inhibits the body's immune response. This makes it play an important protective role in regulating autoimmune tolerance and autoimmune diseases. However, its immunosuppressive effect is also an important factor causing chronic infection and tumor escape.

Research on PD-1 Targeting Drugs in Diseases

Current monoclonal antibodies for PD-1 include nivolumab and pembrolizumab. Targeting PD-1 has been applied in many diseases.

Nivolumab: non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), bladder cancer (BC), microsatellite instability or mismatched repair defect (MSI-H/dMMR) colorectal cancer (CRC), hepatocellular carcinoma (HCC), classic Hodgkin's lymphoma (cHL), melanoma, and head and neck squamous cell carcinoma (HNSCC).

Pembrolizumab: melanoma, HNSCC, cervical cancer, cHL, NSCLC, BC, gastric cancer, and gastroesophageal cancer, as well as all advanced solid tumors classified as MSI-H/dMMR.

More information you may be interested in…

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PDCD1 Proteins for Homo sapiens (Human)


PDCD1 ELISA Kit for Homo sapiens (Human)

PDCD1 ELISA Kit for Mus musculus (Mouse)


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