Author of

• 28971

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  Lunch & Poster Display session (ID 58)

  • Event: ELCC 2019
  • Type: Poster Display session
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 4/11/2019, 12:30 - 13:00, Hall 1

  • 29072

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    138P - PD-L1 confers primary resistance to EGFR-TKI in EGFR mutant non-small cell lung cancer via inducing EMT phenotype (ID 356)

    12:30 - 13:00  |  Author(s): Jianjie Zhu
    • Abstract
    • Slides

    Background
    

    There were approximately 30% of patients with epidermal growth factor receptor (EGFR)-activating mutations do not respond to EGFR- tyrosine kinase inhibitors (TKIs) (primary resistance). However, little is known about the molecular mechanism involved in primary resistance to EGFR-TKIs in EGFR-mutant non-small-cell lung cancer (NSCLC). Programmed death ligand-1 (PD-L1) (B7-H1, CD274) is an important immune co-signaling molecule from the B7/CD28 family, it not only negatively regulates T cell functions through its PD-1 and CD80 interactions, but also plays important regulatory roles in intracellular functions and leads to acquired resistance to EGFR-TKIs in NSCLC. Here, we investigated that mechanistic role of PD-L1 in primary resistance to EGFR-TKIs in EGFR-mutant NSCLC.

    a9ded1e5ce5d75814730bb4caaf49419 Methods
    

    The mRNA expression level of PD-L1 was detected using real-time quantitative reverse transcriptase PCR. Molecular manipulations (overexpression or silencing) were performed to investigate the effect of PD-L1 expression on sensitivity to gefitinib in vitro, and a xenograft mouse model was used for in vivo confirmation. Migration and invasion assay were used to determine EMT phenotype.

    20c51b5f4e9aeb5334c90ff072e6f928 Results
    

    The mRNA expression level of PD-L1 was consistent with IC50 value for gefitinib in H1975, HCC827 and PC-9 cell line. Overexpression of PD-L1 decreased the sensibility to gefitinib, in addition, knockdown of PD-L1 increased the sensibility to gefitinib in vitro. Furthermore, Overexpression of PD-L1 attenuated sensitivity to gefitinib in a xenograft mouse model. Overexpression of PD-L1 leaded to primary resistance to gefitinib through inducing EMT phenotype.

    fd69c5cf902969e6fb71d043085ddee6 Conclusions
    

    PD-L1 contributes to primary resistance to EGFR-TKI in EGFR mutant non-small-cell lung cancer, which may be mediated by inducing EMT phenotype.

    b651e8a99c4375feb982b7c2cad376e9 Legal entity responsible for the study
    

    The First Affiliated Hospital of Soochow University.

    213f68309caaa4ccc14d5f99789640ad Funding
    

    Has not received any funding.

    682889d0a1d3b50267a69346a750433d Disclosure
    

    All authors have declared no conflicts of interest.

    cffcb1a185b2d7d5c44e9dc785b6bb25

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