Programmed death-ligand 1 (PD-L1) also known as cluster of differentiation 274 (CD274) or B7 homolog 1 (B7-H1) is a protein that in humans is encoded by the CD274 gene.
PDL1, CD274 molecule, Programmed cell death ligand 1
Gene location (Human)
Chromosome 9 (human)
RNA expression pattern
Programmed death-ligand 1 (PD-L1) is a 40kDa type 1 transmembrane protein that plays a major role in suppressing the adaptive arm of immune systems during particular events such as pregnancy, tissue allografts, autoimmune disease and other disease states such as hepatitis.
Normally the adaptive immune system reacts to antigens that are associated with immune system activation by exogenous or endogenous danger signals: this in turn, clonally expands antigen-specific CD8+ T cells and/or CD4+ helper cells.
PD-L1 reduces the proliferation of antigen-specific T-cells in lymph nodes, while simultaneously reducing apoptosis in regulatory T cells.
PD-L1 is expressed on both hematopoietic and nonhematopoietic cells in tissues.
PD-L1 binds to its receptor, PD-1, found on activated T cells, B cells, and myeloid cells, to modulate activation or inhibition.
Upon IFN-γ stimulation, PD-L1 is expressed on T cells, NK cells, macrophages, myeloid DCs, B cells, epithelial cells, and vascular endothelial cells.
PD-L1 is notably expressed on macrophages.
PD-L1 is shown to be highly expressed in a variety of malignancies, particularly lung cancer.
In order to anticipate the effectiveness of gene therapy or systemic immunotherapy in blocking the PD-1 and PD-L1 checkpoints, PD-L1 might be employed as a prognostic marker and a target for anti-cancer immunity.
Up regulation of PD-L1 may allow cancers to evade the host immune system.
With renal cell carcinoma high tumor expression of PD-L1 was associated with increased tumor aggressiveness and a 4.5-fold increased risk of death.
In normal tissue, feedback between transcription factors like STAT3 and NF-κB can restrict the immune response to protect host tissue and limit inflammation.
In cancer, loss of feedback restriction between transcription factors can lead to increased local PD-L1 expression, which could limit the effectiveness of systemic treatment with agents targeting PD-L1.
pSTAT-1 and PDL-1 expressions also strongly correlate in prostate cancer activity.
Upregulation of PD-L1 on immune cells can also lead to formation of an immunosuppressive environment in a highly localized manner that also allow the cancer cells to proliferate.
PD-L1 analysis in TNBC is essential for selecting patients eligible for immunotherapy.
Evidence suggests that PD-L1 acts as a positive costimulatory molecule in intracellular infection.
PD-1/PD-L1 interaction is thought to play a role in preventing destructive autoimmunity, especially during inflammatory conditions.
In the stomach, PD-1 expression protects the gastrin expressing G-cells from the immune system during Helicobacter pylori-provoked inflammation.
But also a variety of pre-clinical studies support the notion that the PD-1/PD-L1 interaction is implicated in autoimmunity.
In humans, PD-L1 was found to have altered expression in pediatric patients with systemic lupus erythematosus (SLE).