Author of

• 35377

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  P14 - Immuno-biology and Novel Immunotherapeutics (Phase I and Translational) - Immuno-Biology (ID 153)

  • Event: WCLC 2020
  • Type: Posters
  • Track: Immuno-biology and Novel Immunotherapeutics (Phase I and Translational)
  • Presentations: 1
  • Moderators:
  • Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall

  • 35397

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    P14.12 - MET Amplification and Immune Checkpoint Inhibitor Efficacy in NSCLC (ID 2067)

    00:00 - 00:00  |  Presenting Author(s): shan Su
    • Abstract
    • Slides

    Introduction
    

    Immune checkpoint inhibitors (ICIs) have brought clinical benefits to patients with various histological types of lung cancer, including squamous cell carcinoma and adenocarcinoma, yet the immunotherapy response varies among patients, and the
    need for predictive biomarkers is urgent. Previous studies have shown an association between mesenchymal-epithelial transition (MET) and the immunotherapy response in NSCLC but lack clinical data on the correlation of MET gene amplification with the ICI
    response in NSCLC.

    Methods
    

    Copy number alteration, somatic mutation, and clinical data from two immunotherapy cohorts (patients from the Rizvi et al cohort and our local cohort) were collected and pooled to further investigate the key role of MET amplification in patients with NSCLC receiving ICIs. The correlations between MET amplification and tumor immunogenicity and antitumor immunity were further investigated in The Cancer Genome Atlas (TCGA)-NSCLC (lung adenocarcinoma (LUAD)/lung squamous cell carcinoma (LUSC)) dataset. The correlation between MET amplification and the sensitivity to chemotherapy and targeted drugs was further analyzed in the Genomics of Drug Sensitivity in Cancer (GDSC) database.

    Results
    

    In the immunotherapy cohorts, MET amplification was associated with longer progression-free survival (PFS) times in patients receiving ICI treatment (P=0.039 HR=0.37, 95% CI: 0.18−0.73). In the TCGA-NSCLC dataset, MET amplification was associated with higher MET mRNA and protein levels, tumor mutation burden (TMB),neoantigen load, immune-activated cell patterns and immune-related gene expression levels. The gene set enrichment analysis (GSEA) results indicated significant upregulation of the immune response-related pathways in the MET-amplification group.The number of gene alterations in the DNA damage response and repair (DDR)pathway in the MET-amplification group was significantly higher than that in the nonMET amplification group. In addition, drug sensitivity analysis in the GDSC dataset suggested that the MET-amplification group exhibited resistance to common chemotherapeutic and targeted drugs.

    

    Conclusion
    

    MET amplification was strongly associated with longer PFS times and with known immunotherapeutic response markers, including the TMB, the neoantigen load, immune-related genes, and high infiltration of specific immune cells, suggesting that MET amplification can be used as a novel predictive biomarker in NSCLC immunotherapy.

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