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Increased EGFR Phosphorylation Correlates with Higher Programmed Death Ligand-1 Expression: Analysis of TKI-Resistant Lung Cancer Cell Lines
Joint Authors
Suda, Kenichi
Mitsudomi, Tetsuya
Rozeboom, Leslie
Furugaki, Koh
Yu, Hui
Melnick, Mary Ann C.
Ellison, Kim
Rivard, Christopher J.
Politi, Katerina
Hirsch, Fred R.
Source
Issue
Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-7, 7 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2017-10-08
Country of Publication
Egypt
No. of Pages
7
Main Subjects
Abstract EN
Despite the recent development of immunotherapies that target programmed death-1 (PD-1) or programmed death ligand-1 (PD-L1) in non-small cell lung cancer (NSCLC) treatment, these therapies are less effective in NSCLC patients with epidermal growth factor receptor (EGFR) mutations.
However, the molecular mechanisms underlying this lower efficacy of immunotherapies in EGFR mutant lung cancers are still unclear.
In this study, we analyzed PD-L1 protein expression in lung cancer cell lines with EGFR mutations prior to and after acquisition of resistance to EGFR tyrosine kinase inhibitors (TKIs).
We found that parental lung cancer cell lines harboring EGFR mutations showed negative (PC9 and H3255 cells) and positive (HCC827 cells) staining for PD-L1 by immunohistochemistry.
Comparing PD-L1 expression between EGFR-TKI resistant cell lines and their parental cells, we found that increased phosphorylation of EGFR was related to increased expression of PD-L1.
Increased phosphorylation of EGFR was accompanied by the T790M secondary mutation.
Acquired resistance cells with MET amplification or EGFR loss both showed decreased phosphorylation of EGFR and decreased PD-L1 expression.
Our results indicate that lung cancer cell lines with EGFR mutations (parental cells) do not harbor high PD-L1 protein expression.
In addition, EGFR phosphorylation affects PD-L1 expression after acquisition of resistance to EGFR-TKIs.
American Psychological Association (APA)
Suda, Kenichi& Rozeboom, Leslie& Furugaki, Koh& Yu, Hui& Melnick, Mary Ann C.& Ellison, Kim…[et al.]. 2017. Increased EGFR Phosphorylation Correlates with Higher Programmed Death Ligand-1 Expression: Analysis of TKI-Resistant Lung Cancer Cell Lines. BioMed Research International،Vol. 2017, no. 2017, pp.1-7.
https://search.emarefa.net/detail/BIM-1138701
Modern Language Association (MLA)
Suda, Kenichi…[et al.]. Increased EGFR Phosphorylation Correlates with Higher Programmed Death Ligand-1 Expression: Analysis of TKI-Resistant Lung Cancer Cell Lines. BioMed Research International No. 2017 (2017), pp.1-7.
https://search.emarefa.net/detail/BIM-1138701
American Medical Association (AMA)
Suda, Kenichi& Rozeboom, Leslie& Furugaki, Koh& Yu, Hui& Melnick, Mary Ann C.& Ellison, Kim…[et al.]. Increased EGFR Phosphorylation Correlates with Higher Programmed Death Ligand-1 Expression: Analysis of TKI-Resistant Lung Cancer Cell Lines. BioMed Research International. 2017. Vol. 2017, no. 2017, pp.1-7.
https://search.emarefa.net/detail/BIM-1138701
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1138701