Author of

• 18606

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  P3.03 - Poster Session with Presenters Present (ID 473)

  • Event: WCLC 2016
  • Type: Poster Presenters Present
  • Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
  • Presentations: 1
  • Moderators:
  • Coordinates: 12/07/2016, 14:30 - 15:45, Hall B (Poster Area)

  • 18640

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    P3.03-034 - Comprehensive Immunophenotyping of the Blood and Pleural Fluid from Patients with Malignant Pleural Mesothelioma by Flow Cytometry (ID 6294)

    14:30 - 14:30  |  Author(s): S. Bornschlegl
    • Abstract

    Background:
    Malignant pleural mesothelioma (MM) remains an almost universally fatal disease with limited treatment options. Immunotherapy represents a rapidly emerging therapeutic strategy for multiple malignancies including MM. However durable therapeutic responses occur in a minority (~30%) of patients. Better understanding of the quantities and immunophenotype of circulating and intrapleural immune cells is essential to design and apply personalized immunotherapeutic strategies.
    
    Methods:
    We used a comprehensive flow cytometry panel (PLoS One. 2015 Mar 23;10 (3):e0121546) to prospectively characterize circulating and pleural fluid immune cells in patients with MPM (n=12) and normal volunteers (circulating cells only, n=50). Matched blood and pleural samples were available from 11 patients, including samples from 9 patients enrolled into a Phase I study investigating the intrapleural administration of the modified vaccine strain measles virus (MV-NIS), MC1023. Pre- and post-treatments samples were available from 7 patients. The immune cell counts and cell fractions were compared using a false discovery rate (FDR) of 10% and the non-parametric Mann-Whitney test and the Wilcoxon matched-pairs signed rank test (blood versus pleural fluid and different time points). (p ≤ 0.05)
    
    Results:
    Cell counts and immune phenotype of circulating immune cells differ between of patients with MPM differ from normal volunteers (31 of 86 cell types). Patients with MPM had fewer B-lymphocytes, more pro-inflammatory monocytes (CD14+CD16+) and exhausted CD4 and CD8 T-lymphocytes (CD4 and CD8 PD1+TIM3+ double positive cells). As expected we observed characteristic differences between blood and pleural fluid in MPM patients. For example there are a higher numbers of antigen experienced, PD-1 expressing CD4 and CD8-memory cells within the pleural fluid compared to the peripheral blood. The intrapleural administration of a modified vaccine strain measles (MV-NIS) triggered changes in pleural and circulating immune cells. While these changes varied among patients, we observed increased CD80 and CD86 expression on CD14+ monocytes in the pleural fluid down.
    
    Conclusion:
    Comprehensive flow-cytometric immunophenotying of blood and pleural fluid is feasible in patients with MPM. This approach may help to identify patients who may respond favorably to specific immunotherapeutic interventions such as immune checkpoint inhibitors or facilitate longitudinal immune monitoring during clinical trials. Additional data is needed and we are continuing to prospectively analyze samples from patients with MPM.