Virtual Library

Start Your Search

Heidar Albandar



Author of

  • +

    P2.04 - Immuno-oncology (ID 167)

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

      P2.04-26 - Single Cell Proteomics Profiling of Live T-Cells in KRAS+ and MET-Amp NSCLC to Predict Immune Checkpoint Inhibitor Response (Now Available) (ID 2279)

      10:15 - 18:15  |  Author(s): Heidar Albandar

      • Abstract
      • Slides

      Background

      Immune checkpoint inhibitors (CPI), alone or in combination with chemotherapeutics, have been approved for first-line treatment in non-small cell lung cancers (NSCLCs) and have therapeutic efficacy across many cancer types. While these new cancer immunotherapeutic agents (e.g. pembrolizumab, nivolumab, atezolizumab) represent exciting additions to the treatment paradigm of a large array of genomics-guided precision medicine strategies for oncogene-addicted lung cancers, emerging clinical data raises doubts about the efficacy and the role of immune checkpoint inhibition in oncogene-addicted lung cancers driven by EGFR mutation, ALK-rearrangement, and MET amplification (MET-Amp) or MET exon-14 skipping mutations, regardless of the expression level of PD-L1. Moreover, clinically relevant and reliable predictive biomarkers of CPI response remain inadequate, despite the currently used PD-L1 expression, tumor mutational burden and microsatellite instability (MSI) status.

      Method

      We longitudinally profiled more than 32 cytokines released by peripheral T-lymphocytes from patients under CPI therapy using a novel live single-cell microfluidics-based liquid biopsy platform. Paired pretreatment and post-2 cycles of treatment peripheral blood samples from each subject were analyzed to delineate early biomarkers correlative to CPI treatment response in a pilot cohort of four representative patients with advanced NSCLC.

      workflow.png

      Result

      CD8(+) T-cells have stronger polyfunctional response than CD4(+) T-cells in all patients, demonstrating considerable heterogeneity among different patients and different T-cell types [CD4(+) vs. CD8(+)]. To compare overall polyfunctional upregulation by cytokines grouped by function, we adopted a novel polyfunctional strength index (PSI) in our biomarker bioinformatics analysis. Post-treatment CD4(+)/CD8(+) T-cells across patients showed overall higher PSI than pretreatment cells except in one patient. The polyfunctional profiles are largely composed of effector proteins associated with antitumor immunity and, to a lesser extent, chemoattractive and regulatory cytokines in CD8(+) T-cells. Upon anti-CD3/CD28 stimulation, the combinations of secreted cytokines in post-treatment samples are markedly distinct from pretreatment samples in both CD4(+) and CD8(+) cell subsets. The PSI analysis data presented highlight a patient with stage IVB KRAS-mutated (KRAS+)(PD-L1=60%) lung adenocarcinoma and another one with MET-amplified lung adenocarcinoma (PD-L1=85%-95%), who demonstrated excellent tumor response to anti-PD1 CPI, providing an immune single cell proteomics biomarker measure of response in oncogene-addictive tumor treated under CPI.

      Conclusion

      Our study nominated an early association between single-cell immune cytokine profiling and CPI clinical treatment outcome in advanced oncogene-driven NSCLC. Further studies with larger cohorts are warranted for validating PSI as predictive biomarker of CPI response, especially in patients with addictive oncogene-driven lung cancer.

      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.