Virtual Library

Start Your Search

K. Kashiwabara

Author of

  • +

    MA15 - Immunotherapy Prediction (ID 400)

    • Event: WCLC 2016
    • Type: Mini Oral Session
    • Track: Chemotherapy/Targeted Therapy/Immunotherapy
    • Presentations: 1
    • +

      MA15.01 - Immunogram for Cancer-Immunity Cycle towards Personalized Immunotherapy of Lung Cancer (ID 4519)

      14:20 - 15:50  |  Author(s): K. Kashiwabara

      • Abstract
      • Slides

      The interaction of immune cells and cancer cells shapes the immunosuppressive tumor microenvironment. For successful cancer immunotherapy, comprehensive knowledge of anti-tumor immunity as a dynamic spacio-temporal process is required for each individual patient. To this end, we developed an "immunogram for the cancer-immunity cycle" using next-generation sequencing.

      Whole-exome sequencing and RNA-Seq were performed in 20 non-small cell lung cancer patients (12 adenocarcinoma, 7 squamous cell carcinoma, and 1 large cell neuroendocrine carcinoma). Mutated neoantigens and cancer-germline antigens expressed in the tumor were assessed for predicted binding to patients’ HLA molecules. The expression of genes related to cancer-immunity was assessed and normalized; immunogram was drawn in a radar chart composed of 8 axes reflecting 7 steps of cancer-immunity cycle.

      Distinctive patterns of immunogram were observed in lung cancer patients: T-cell-rich and T-cell-poor. Patients with T-cell-rich pattern had gene signatures of abundant T cells, Tregs and MDSCs, checkpoint molecules and immune-inhibitory molecules in the tumor, suggesting the presence of counter regulatory immunosuppressive microenvironment. Unleashing of counter regulations, i.e. checkpoint inhibitors, may be indicated for these patients (Figure A). Immunogram of T-cell-poor phenotype reflected lack of anti-tumor immunity, inadequate DC activation, and insufficient antigen presentation in the tumor (Figure B). When the immunograms were overlaid within each tumor histology, no typical pattern was elucidated. Both T-cell-rich and T-cell-poor phenotypes were present in each histology, suggesting that histology cannot necessarily reflect the cancer-immunity status of the tumor (Figure C,D). These results were consistent with previous studies showing that clinical responses of checkpoint blockade were not easily predicted by the histology. Figure 1

      Utilizing the immunogram, the landscape of the tumor microenvironment in each patient can be appreciated. Immunogram for the cancer-immunity cycle can be used as an integrated biomarker and thus may become a helpful resource toward optimal personalized immunotherapy.

      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.