programmed cell death 1 ligand 1

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Ligands
programmed cell death 1 ligand 1 (Human)

GtoPdb Ligand ID: 9606

Abbreviated name: PD-L1

Synonyms: B7 homolog 1 | B7-H1 | PDL1 | programmed death ligand 1

Compound class: Endogenous peptide in human, mouse or rat

Comment: This is one of the ligands for the PD-1 receptor. It is a single-pass type I membrane protein. The PD-L1/PD-1 interaction is an established immune checkpoint. Both the ligand and receptor are targets for novel immuno-oncology therapeutics, as over-expression of either of these proteins is a mechanism used by tumour cells to evade immune detection and destruction. Already the target of approved immunotherapeutics in the form of monoclonal antibodies, small molecules targeting the PD-1/PD-L1 checkpoint are now in development to address the shortcomings associated with the current antibody therapies (including, poor susceptibility rate to single immune checkpoint pathway inhibitors, long half-life of antibodies and association with the development of adverse events, problems connected to the requirement for intravenous infusions) [7,16].

Species: Human

Immunopharmacology Comments
PD-L1 is an endogenous ligand of the checkpoint receptor programmed cell death 1 (PD-1). Engagement of PD-1 by PD-L1 has immunosuppressive action. PD-L1 is expressed by macrophages, monocytes, granulocytes, NK cells, dendritic cells, T cells and B cells. Both the ligand and receptor are pharmacological targets for novel immuno-oncology therapeutics, as over-expression of either of these proteins is a mechanism used by tumour cells to evade immune detection and destruction. Antibody-based therapies targeting the PD-1/PD-L1 pathway augment immune responses and eliminate tumour-induced tolerance. Clinically this action has been observed as regression in various tumour types, including melanoma, renal cell carcinoma [6] and non-small cell lung cancer [3-4]. The first anti-PD-L1 therapeutic, atezolizumab, was approved for use in 2016 (metastatic urothelial carcinoma and locally advanced or metastatic non-small cell lung cancer unresponsive to platinum therapy, harbouring EGFR or ALK gene abnormalities). As of July 2017, there are 3 anti-PD-L1 biologic therapies that are FDA approved for clinical use; atezolizumab, durvalumab and avelumab.

Immunopharmacology Comments

PD-L1 is an endogenous ligand of the checkpoint receptor programmed cell death 1 (PD-1). Engagement of PD-1 by PD-L1 has immunosuppressive action. PD-L1 is expressed by macrophages, monocytes, granulocytes, NK cells, dendritic cells, T cells and B cells.

Both the ligand and receptor are pharmacological targets for novel immuno-oncology therapeutics, as over-expression of either of these proteins is a mechanism used by tumour cells to evade immune detection and destruction. Antibody-based therapies targeting the PD-1/PD-L1 pathway augment immune responses and eliminate tumour-induced tolerance. Clinically this action has been observed as regression in various tumour types, including melanoma, renal cell carcinoma [6] and non-small cell lung cancer [3-4]. The first anti-PD-L1 therapeutic, atezolizumab, was approved for use in 2016 (metastatic urothelial carcinoma and locally advanced or metastatic non-small cell lung cancer unresponsive to platinum therapy, harbouring EGFR or ALK gene abnormalities). As of July 2017, there are 3 anti-PD-L1 biologic therapies that are FDA approved for clinical use; atezolizumab, durvalumab and avelumab.

Immunopharmacology Disease
Disease	X-Refs	Comment	References
Vitiligo	Disease Ontology: DOID:12306 OMIM: 193200	PD-L1 fusion protein treatment has been shown to increase Treg abundance and reduce/reverse depigmentation development in Pmel-1 vitiligo mice.	13