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Christopher Wae Keong Szeto



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    P3.04 - Immunooncology (Not CME Accredited Session) (ID 970)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.04-14 - TMB and Immune Checkpoint Inhibitor Gene Expression are Unrelated in NSCLC Patients (ID 14218)

      12:00 - 13:30  |  Presenting Author(s): Christopher Wae Keong Szeto

      • Abstract
      • Slides

      Background

      Tumor Mutation Burden (TMB) is an emerging biomarker for response to immune checkpoint inhibitor therapy (ICT). PDL1 is still the only companion diagnostic test for ICT. We sought to examine the relationship between TMB based on whole exome sequencing (WES) data and ICT gene expression.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Retrospective analysis of a database from a commercial DNA tumor:normal and RNAseq platform was carried out. 112 samples were identified with tumor and normal DNA sequencing (WGS or WES) and RNA sequencing. A “high” vs “low” mutation burden was defined with a threshold of 200 exonic non-synonymous mutations. ICT gene expression of 12 checkpoint markers (CTLA4,IDO,FOXP3,LAG3,TIGIT,VEGFA,VEGFC,VEGFB,PDL2,PDL1,OX40, & TIM3) were analyzed for tissue-specific enrichment and within the TMB high and low categories. Immune-cell infiltration was estimated using RNA deconvolution based on known immune cell marker genes (Bindea et al 2013).

      4c3880bb027f159e801041b1021e88e8 Result

      52 of the 112 patients had high TMB based on the defined threshold. ICT gene expression was not significantly different in the TMB high and low groups and none of the 12 ICT markers showed a significant correlation with TMB. Age and gender did not affect TMB.

      checkpoints_vs_tmb.png

      8eea62084ca7e541d918e823422bd82e Conclusion

      Quantitative TMB may be a marker of ICT efficacy independent of ICT gene expression.

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