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Sandeep Reddy



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    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
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      P2.04-64 - 222 NSCLC’s Classified by PAM50: Luminal A NSCLC Is a Distinct Subtype with Low TMB and Immune Suppressive TME (ID 1797)

      10:15 - 18:15  |  Author(s): Sandeep Reddy

      • Abstract

      Background

      Breast Cancer (BC) and NSCLC are heterogeneous diseases with distinct disease subtypes. A 50-gene qPCR assay (PAM50) identifies 5 intrinsic biological subtypes: luminal A, luminal B, HER2-enriched, basal-like, and normal-like breast cancer. NSCLC subtypes are often divided by driver oncogene mutations. We assessed the association of genomic and transcriptomic patterns in molecular NSCLC subtypes using a 50-gene breast cancer classifier.

      Method

      Retrospective analysis on Whole exome (WES) DNA and deep whole transcriptomic sequencing (RNA-Seq) (∼200x106 reads per tumor) data from NantHealth was done. BC intrinsic subtype sorting based on RNAseq assay was used to classify breast tumors into luminal A, luminal B, HER2-enriched, basal-like, or normal-like. Immune Checkpoint therapy (ICT) gene expression was measured for PDL1,CTLA4,LAG3, IDO,TIM3,OX40,FOXP3,TIGIT, and PDL2.

      Result

      A total of 222 NSCLC patients were classifiable using RNAseq. The molecular BC subtype distribution was 38.74% Luminal A, 32.88% Luminal B, 14.41% HER2-enriched, 9.46% basal-like, and 4.50% normal-like. Using a TMB cutoff of 200 Non-synonymous variants (Rizvi et al), there was a significant difference between LumA and LumB (OR 0.39, p=0.0014) for TMB high v low, which is similar in BC, with LumA v LumB (OR 0.46, p=0.014). In the TMB low LumA group there was a 23% EGFR mut+ rate, with 0 EGFR mut+ in the LumA TMB high group. ICT gene expression showed no difference in PDL1 expression between subgroups, but TIM3 was significantly higher in LumA and lower in Basal. ICT co-expression patterns in LumA suggest TME suppression via TIM3, IDO, and OX40 expression. Gender difference did not affect subtype classification distribution.

      Conclusion

      In this retrospective analysis of NSCLC using PAM50 classification we found similar subtype distributions as BC with both LumA BC and LumA NSCLC subtype as a distinct subgroup characterized by low TMB, and LumA NSCLC with high EGFR mutation frequency, and ICT suppressive TME, suggesting potential uses of the 50 gene BC classifier in NSCLC trial design and treatment for checkpoint inhibitor eligible patients.