Virtual Library

Start Your Search

Reid McNeil



Author of

  • +

    P2.04 - Immuno-oncology (ID 167)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Immuno-oncology
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
    • +

      P2.04-30 - Seq-ing a Better Way to Detect PD-L1 in NSCLC (ID 2534)

      10:15 - 18:15  |  Author(s): Reid McNeil

      • Abstract

      Background

      Immunotherapies targeted against PD-L1 and PD-1 have caused a paradigm shift in the treatment of NSCLC, and PD-L1 protein expression has emerged as a standard diagnostic biomarker that predicts which patients are more likely to respond to immunotherapy. However, the use of PD-L1 protein expression as a biomarker is complicated by differences in PD-L1 antibodies, immunohistochemistry methods and platforms, pathologist scoring, and positivity cut-points. We propose that using RNA-sequencing (RNA-seq) methodologies will be an equally reliable approach to determine PD-L1 expression within a tumour and will yield a greater depth of biomarker information than PD-L1 IHC alone.

      Method

      We performed quantitative immunohistochemistry (qIHC) on 262 resected stage I-III formalin-fixed paraffin-embedded (FFPE) NSCLC patient samples registered in the Glans-Look Lung Cancer Research (GLR) database using the commercially available E1L3N PD-L1 antibody (Cell Signalling Technologies). Staining intensity was quantified and used to establish a positivity threshold that was subsequently used to define positivity cut-points of <1%, 1%-49%, and >50% (as used for determining treatment eligibility for Pembrolizumab). We performed single-end RNA-sequencing on FFPE samples from the same GLR patient cohort. Raw counts were normalized to counts-per-million for use in our analyses.

      Result

      We compared the PD-L1 mRNA expression to the PD-L1 protein staining intensity across the tissue core and found a significant correlation (p<0.001, Spearman’s rho=0.538). We also found significant correlation between PD-L1 mRNA expression and the percent-positivity score determined by qIHC (p<0.001, Spearman’s rho=0.605), which was particularly apparent when comparing PD-L1 mRNA expression between cut-point groups where expression was significantly higher in the 1%-49% and >50% groups. Interestingly, we also found moderate, yet significant correlation between PD-1 mRNA expression and both PD-L1 protein staining intensity and percent positivity (p<0.001, Spearman’s rho=0.437 and 0.415 respectively), and we were able to identify several differentially expressed genes between the PD-L1 positive and negative groups.

      Conclusion

      Given the high degree of correlation between PD-L1 mRNA expression and PD-L1 protein staining and positivity, RNA-seq can be a viable option for assessing candidacy for immunotherapy. In addition to the wealth of supplementary data on important biomarkers, RNA-seq offers the possibility for using non-invasive procedures such as liquid biopsy to measure PD-L1 levels in a sequential, objective fashion.