title: The EGFR pathway is involved in the regulation of PD-L1 expression via the IL-6/JAK/STAT3 signaling pathway in EGFR-mutated non-small cell lung cancer.
abstract: Negative regulation of the signal mediated by the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) pathway can effectively inhibit the function of T and B cells, which play a key role in the regulation of immune response. Recently, emerging evidence has suggested that the expression of PD-L1 is related to the mutation status of the epidermal growth factor receptor (EGFR). Moreover, the activation of the EGFR signaling pathway can induce expression of PD-L1. In the present study, we demonstrated that activated EGFR can upregulate the expression of PD-L1 through the interleukin 6/Janus kinase/signal transducer and activator of transcription 3 (IL-6/JAK/STAT3) signaling pathway in non-small cell lung cancer (NSCLC) cells. Cells treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) can downregulate the activation of the IL-6/JAK/STAT3 pathway, which subsequently reduces the expression of PD-L1. Furthermore, silencing of PD-L1 expression in NSCLC cells correlated with inhibition of cell proliferation and enhanced tumor cell apoptosis. In summary, our research indicates that EGFR is involved in the regulation of PD-L1 expression and cell proliferation via the IL-6/JAK/STAT3 signaling pathway in NSCLC. The present study suggests the potential of combined targeted therapy with immunotherapy in the treatment of NSCLC.
authors: Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors: Nan
authors: N
authors: Zhang
authors: Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors: Yuanyuan
authors: Y
authors: Zeng
authors: Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors: Wenwen
authors: W
authors: Du
authors: Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors: Jianjie
authors: J
authors: Zhu
authors: Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors: Dan
authors: D
authors: Shen
authors: Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors: Zeyi
authors: Z
authors: Liu
authors: Department of Respiratory Medicine, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
authors: Jian-An
authors: JA
authors: Huang
mesh_terms: D060890:B7-H1 Antigen / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D053612:Janus Kinases / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics*; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D047428:Protein Kinase Inhibitors; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D053612:Janus Kinases