The Protein Expression of PDL1 Is Highly Correlated with Those of eIF2α and ATF4 in Lung Cancer

Figure 1

PDL1 expression can be upregulated by oncogenic signaling or the IFNγ/STAT1/IRF1 pathways. IRF1 expression can be upregulated by type I and type II IFN, NF-κB, and DNA damage. The binding of IFNα to IFNAR1/IFNAR1 leads to the formation of ISGF3 (a heterotrimer of STAT1, STAT2, and IRF9) which can upregulate the expression of PD1 and IRF7. The binding of PD1 to PDL1 can have reverse signaling that upregulates IDO1 which can cause phosphorylation of eIF2α. The phosphorylated eIF2α can activate ATF4 which can upregulate the expression of UPR/ISR target genes and inhibit the activity of IRF7. IRF7 can upregulate the expression of ATF4 and IFNα. ATF4, activating transcription factor 4; eIF2α, eukaryotic translation initiation factor 2; IDO1, indoleamine 2,3-dioxygenase 1; IFN, interferon; IFNAR, interferon alpha/beta receptor; IRF, interferon regulatory factor; ISGF3, interferon-stimulated gene factor 3; PD1, programmed death 1; PDL1, programmed death ligand 1; STAT, signal transducer and activator of transcription.