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Chad Garner



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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: 2
    • 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  |  Author(s): Chad Garner

      • 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.

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      8eea62084ca7e541d918e823422bd82e Conclusion

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

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      P3.04-15 - IDO and Tim3 Gene Expression is Correlated in NSCLC Patients with Low PDL1 Gene Expression (ID 14207)

      12:00 - 13:30  |  Author(s): Chad Garner

      • Abstract

      Background

      Background: Tumor cells evade immunosurveillance by expression of immune checkpoint proteins PD-L1, IDO, and TIM3, even when tumor-infiltrating lymphocytes (TILs) are present. Combination of checkpoint inhibitors Pembrolizumab(PD-1i) and Epacadostat (IDOi) failed to show synergy in melanoma. Yet there are several candidate targets for checkpoint inhibition and rational selection of which combinations to explore is lacking. In particular, which checkpoints to target when PD-L1 is not expressed is largely unexplored. The purpose of this study was to assess the expression of 12 immune checkpoint genes in lung cancer patients with high and low expression of PD-L1.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Methods: Retrospective review of deep whole transcriptomic sequencing (RNA-Seq) (∼200x106 reads per tumor) on 1467 unselected clinical cases from NantHealth. 112 NSCLC cases were categorized as PD-L1-low and PD-L1-high by median splitting. Expression and co-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 PD-L1-defined categories. Immune-cell infiltration was estimated using RNA deconvolution based on known immune cell marker genes (Bindea et al 2013).

      4c3880bb027f159e801041b1021e88e8 Result

      Results: CTLA, TIGIT and FOXP3 showed high correlations across all 112 samples as well within the PD-L1 low and high expression groups and differential expression across the two groups, with higher expression of the markers among the PD-L1 high expression group versus the low group. Within the PD-L1 high expression group, the expression of markers LAG3, TIM3, OX40, FOXP3, CTLA4 and TIGIT was both higher and more highly correlated than in the PD-L1 low group. Within the PD-L1-low category, IDO1 and TIM3 have relatively high expression and are highly correlated with each other (R=0.72, p=3.85x10^-10).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Conclusions: PD-L1 is a primary driver of immune suppression, however when PD-L1 is low there may be some differential role for IDO or TIM3. Combination IDOi and Tim3i should be considered in PD-L1 low patients.

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