Skip to main content
. 2020 Oct 26;12(11):3129. doi: 10.3390/cancers12113129

Figure 1.

Figure 1

Regulation of PD-L1 expression involved several factors at different levels. The main extrinsic factors involved in PD-L1 regulation are pictured on the top of the picture and include cytokines (e.g., IFN-γ), growth factors (e.g., EGF), hypoxia, chemotherapy, radiation therapy and TKIs, which regulate PD-L1 expression on the transcriptional level. Among intrinsic factors, genetic alterations, involve intracellular signaling pathways (e.g., MAPK, PI3K/Akt/mTOR, JAK/STAT), tumor suppressor genes (e.g., TP53, STK11), DDR genes (e.g., BRCA1-2, ATM, ATR) and transcription factors (e.g., c-Myc, NF-κB). Other intrinsic factors include epigenetic modifications: CD274 promoter methylation, inhibition of histone deacetylase and regulation of gene translation by miRNAs. The main post-translational modifications able to regulate PD-L1 stability and expression are phosphorylation, ubiquitination, glycosylation and palmitoylation (pictured on the right-hand side). Created with BioRender.com. EGF: Epidermal Growth Factor; EGFR: Epidermal Growth Factor receptor; EML4-ALK: echinoderm microtubule-associated protein-like 4 gene-anaplastic lymphoma kinase gene; IFN-γ: interferon-gamma; IFN-γR: interferon-gamma receptor; TGF-β1: tumor growth factor beta 1; TKIs: tyrosine kinase inhibitors; VEGF: vascular endothelial growth factor; PD-1: programmed-cell death; PD-L1: programmed-cell death ligand 1; TUSC2: tumor suppressor candidate 2; PI3K: phosphatidylinositol 3-kinase; Akt: Protein kinase B; mTOR: mammalian target of rapamycin; JAK: Janus kinase; STAT: signal transducer and activator of transcription; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; TP53: Tumor protein p53; STK11: Serine/threonine kinase 11; DDR: DNA damage response and repair; BRCA1-2: breast cancer type 1 and 2 susceptibility proteins; ATM: Ataxia Telangiectasia Mutated; ATR: ATM related protein; RAS: Rat Sarcoma Viral Oncogene Homolog; MEK: Mitogen-activated ERK kinase; ERK: Extracellular signal-Regulated Kinases; AMPK: 5′ AMP-activated protein kinase; PTEN: Phosphatase and tensin homolog; AP1: Activator protein 1; DNMT1: DNA methyl-transferase 1; IRF: interferon regulatory factor; Me: methyl group, P: phosphate group, STING: stimulator of interferon genes; HIF-1α: Hypoxia-inducible factor 1-alpha, HRE: hypoxia-response element, HDAC: Histone deacetylase; HDACi: Histone deacetylase inhibitors; EMT: epithelial–mesenchymal transition; GSK3β: glycogen synthase kinase 3beta.