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W.T. Vigneswaran



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    OA13 - Immunotherapy in Malignant Pleural Mesothelioma: Current Status of Trials and New Approaches (ID 392)

    • Event: WCLC 2016
    • Type: Oral Session
    • Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
    • Now Available
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      OA13.05 - Somatic Genetic Alterations and Immune Microenvironment in Malignant Pleural Mesothelioma (Now Available) (ID 5087)

      W.T. Vigneswaran

      • Abstract
      • Presentation
      • Slides

      Background:
      The genomic landscape of malignant pleural mesothelioma (MPM) is not well understood. Advanced high-throughput sequencing technologies allow comprehensive characterization of genetic alterations. Knowledge of the somatic mutations and the immune microenvironment in patients with MPM will help to develop effective targeted therapies.

      Methods:
      We examined biopsy specimens from 12 MPM patients (8 epithelioid and 4 biphasic) that were removed during maximal cyto-reductive surgery. Specimens from 3 different sites (anterior, posterior and diaphragm, a total of 36 tissue samples) were studied through whole exome sequencing, T cell receptor (TCR) repertoire analysis of tumor-infiltrating T cells (TILs), and expression levels of immune-related genes. We also performed in silico prediction of potent neoantigens derived from non-synonymous somatic mutations in each specimen. For the comparison of tumor tissues from 3 different sites, we performed hierarchical clustering to assess the tumor heterogeneity and differences in immune environment.

      Results:
      High mutation/neoantigen load was significantly correlated with higher clonal expansion of TILs (R=0.46) and high expression levels of immune-associated cytolytic factors, granzyme A (R=0.25) and perforin 1 (R=0.48), in tumor tissues. In the clustering analysis, heterogeneous MPM cases revealed unique neoantigens and clonotypes of TILs that were restricted to each of tumor site, suggesting infiltration of the neoantigen-specific T cells. Further sub-analysis according to histologic types showed that biphasic tumors had higher mutation/neoantigen load and stronger oligo-clonal T cell expansion (p=0.01) than epithelioid tumors.

      Conclusion:
      Our analysis demonstrated a significant correlation between somatic mutation/neoantigen load, clonality of TILs, and the immune-related tumor microenvironment in MPM. Our findings suggest that high mutation/neoantigen load in tumor cells might promote effective expansion and infiltration of functional (tumorocidal) T cells into the tumor bed. These findings provide a rationale for selecting MPM patients who can benefit from treatment with immune checkpoint blockades. This may accelerate development of the neoantigen targeting TCR-engineered T cell therapy for MPM.

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    WS04 - Mesothelioma Workshop (Ticketed Session) (ID 416)

    • Event: WCLC 2016
    • Type: Workshop
    • Track: Mesothelioma/Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 12/04/2016, 08:00 AM - 11:00 AM, Stolz 2
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      WS04.03 - Debate - Induction Chemotherapy is Better than Postoperative Adjuvant Therapy for Early Stage Pleural Mesothelioma (Now Available) (ID 6985)

      W.T. Vigneswaran

      • Abstract
      • Presentation
      • Slides

      Abstract not provided

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