title: EGFR-TKI down-regulates PD-L1 in EGFR mutant NSCLC through inhibiting NF-κB.
abstract: Non-small-cell lung cancer (NSCLC) is a severe disease threatening human health. Targeted therapy of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has obtained potent efficacy in the treatment of NSCLC patients. However, the effects of EGFR-TKIs on tumor immune microenvironment are unclear. In this study, we show that NSCLCs with EGFR mutation express higher programmed cell death ligand 1 (PD-L1) than NSCLCs with wild type EGFR. The EGFR activation is also associated with high expression of PD-L1. The EGFR-TKI gefitinib can reduce PD-L1 expression, via inhibiting NF-κB, in EGFR mutant NSCLC in vitro and in vivo. These findings elucidate a novel anti-tumor mechanism of EGFR-TKI and provide the possibility of combined strategy of targeted therapy and immunotherapy for EGFR mutant NSCLC patients.
authors.affiliation: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Kailong
authors.initials: K
authors.lastname: Lin
authors.affiliation: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Jianan
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.affiliation: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Institute of Cancer, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: b.davis.zhu@gmail.com.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D060890:B7-H1 Antigen / Q000235:genetics* / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D015536:Down-Regulation / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D006801:Humans; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000235:genetics; D059016:Tumor Microenvironment / Q000187:drug effects / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D060890:B7-H1 Antigen; C423236:CD274 protein, human; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C498143:RELA protein, human; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D051996:Transcription Factor RelA; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
keywords: EGFR-TKI; NF-κB; NSCLC; PD-L1