Author of

• 25941

  +

  P2.04 - Immunooncology (Not CME Accredited Session) (ID 953)

  • Event: WCLC 2018
  • Type: Poster Viewing in the Exhibit Hall
  • Track:
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall

  • 26980

    +

    P2.04-05 - Correlation Between PD-L1 Gene Promoter Polymorphisms and Expression of PD-L1 mRNA and Protein in NSCLC Patients. (ID 12554)

    16:45 - 18:00  |  Author(s): Tomasz Kucharczyk
    • Abstract
    • Slides

    Background
    

    Immunotherapy, the most novel approach to cancer treatment, gives a promising option for non-small cell lung cancer (NSCLC) patients. Most drugs targeting PD-1 or PD-L1 have been proven to be effective when cancer tissue expresses PD-1 or PD-L1 protein on its surface. The promoter region of PD-L1 gene is responsible for regulating the gene expression, thus in effect the expression of the protein. We decided to check whether single nucleotide polymorphisms (SNPs) in PD-L1 gene promoter region may affect this expression.

    a9ded1e5ce5d75814730bb4caaf49419 Method
    

    The study included 47 NSCLC patients (20 male, 27 female; median age 65±7.6 ). PD-L1 protein expression was analysed using two IHC assays with SP142 and 22C3 antibodies, on corresponding analysis platforms. mRNA was analysed using qRT-PCR method. PD-L1 gene promoter region polymorphisms [rs822335(C/T) and rs822335(C/G)] were analysed using real-time PCR method, on Illumina Eco platform. The analysis was performed in histological (resected tissue) and cytological (cellblocks from bronchoscopy biopsies) material (FFPE blocks).

    4c3880bb027f159e801041b1021e88e8 Result
    

    There were significant positive correlations between expression of mRNA of PD-L1 gene and the percentage of PD-L1 protein positive cells: tumor cells in the reaction with 22C3 antibody (R=+0.39,p=0.025), tumor cells in the reaction with SP142 antibody (R=+0.45, p=0.009) as well as infiltrating immune cells in the reaction with SP142 antibody (R=+0.49, p=0.006).

    The studied group consisted of 21 CC homozygotes, 23 CT heterozygotes and 3 TT homozygotes in rs822335, and 12 CC homozygotes, 24 CG heterozygotes and 11 GG homozygotes in rs822336 polymorphic sites.

    Slightly higher (p=0.08) percentage of tumor cells with PD-L1 expression was observed in patients with CC genotype compared to patients with CT and TT genotypes in rs822335 polymorphism. We observed significantly higher expression of mRNA for PD-L1 gene in patients with GG genotype compared to patients with CG genotype (p=0.05) in rs822336 polymorphism. Additionally, odds ratio analysis showed that a higher chance of high mRNA expression of PD-L1 gene occurred in patients with GG genotype as compared to patients with CC genotype (OR=7.0, ch²=4.46, p=0.035).

    8eea62084ca7e541d918e823422bd82e Conclusion
    

    Analysis of PD-L1 expression on tumor cells presents numerous problems – availability of material, tumor heterogeneity, different methods of detection. We have presented that analysis of PD-L1 gene promoter polymorphisms may be useful in determination of PD-L1 expression. It might be carried out in blood samples, when surgical material is not available. The usefulness of PD-L1 gene polymorphism, as a predictor of immunotherapy, should be investigated in clinical trials.

    6f8b794f3246b0c1e1780bb4d4d5dc53

    Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.