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Takahiro Karasaki



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    P1.07 - Immunology and Immunotherapy (ID 693)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Immunology and Immunotherapy
    • Presentations: 1
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      P1.07-017 - Assessment of Cancer Immunity Status in Each Patient Using Immunogram (ID 9115)

      09:30 - 16:00  |  Presenting Author(s): Takahiro Karasaki

      • Abstract
      • Slides

      Background:
      For successful cancer immunotherapy, comprehensive profiling of cancer-immune system interaction is required for each individual patient. To this end, we developed an immunogram reflecting the cancer immunity cycle and applied it to real patients with lung cancer.

      Method:
      Whole-exome sequencing and RNA-Seq were performed in 25 non-small cell lung cancer patients (13 adenocarcinoma, 11 squamous cell carcinoma, and 1 large cell neuroendocrine carcinoma). The number of somatic mutations and the expression of genes related to cancer-immunity were assessed and normalized using TCGA-LUAD and LUSC data (n=1035). Immunogram of each patient was drawn in a radar chart composed of 9 axes reflecting 7 steps of cancer-immunity cycle.

      Result:
      Various patterns of immunogram were observed in all 25 lung cancer patients, suggesting that each patient has their own pattern of immunosuppressive microenvironment (Figure 1). The hierarchical clustering using each scores of immunogram showed four clusters of patients characterized by T cell phenotype (inflamed vs non-inflamed) and tumor antigenicity (high vs low) (Figure 2). T cell-inflamed tumors (Clusters 3&4) had gene signatures of abundant T cells and interferon gamma (IFNG) response, as well as inhibitory cells and checkpoint molecules, suggesting the presence of counter regulatory immunosuppressive microenvironment. Unleashing of counter regulations by checkpoint inhibitors, for example, may be indicated for these patients. Each scores of immunogram had no correlation with histology. This result was consistent with previous studies of checkpoint blockade that clinical responses were not easily predicted solely by the histology. Patient age, gender and TNM stage also did not correlate with each immunogram scores. Figure 1



      Conclusion:
      The landscape of the tumor microenvironment in each patient can be appreciated by utilizing immunogram. Immunogram for the cancer-immunity cycle can be used for the assessment and visualization of cancer immunity status in each patient, and thus may become a helpful resource toward optimal personalized immunotherapy.

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    P3.16 - Surgery (ID 732)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Surgery
    • Presentations: 1
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      P3.16-028 - Necrosis Is a Predictor of Recurrence in Patients with Small Lung Adenocarcinoma ≦2cm (ID 10451)

      09:30 - 16:00  |  Author(s): Takahiro Karasaki

      • Abstract

      Background:
      The prognostic significance of pathological necrosis in small lung adenocarcinoma has not been investigated. The purpose of this study is to investigate the prognostic role of pathological necrosis in patients with completely resected small lung adenocarcinoma ≦2cm.

      Method:
      All available tumor slides from patients with surgically resected lung adenocarcinoma ≦2cm in size (1998-2015) were retrospectively reviewed. Exclusion criteria: patients who received induction therapy and lung cancer surgery within preceding 2 years. Recurrence free probability and overall survival were assessed using the Kaplan-Meier method.

      Result:
      351 patients met inclusion criteria (48% women, median age 67yr (34-86 yrs), 50% never-smokers; 324 Stage IA, 27 Stage IB; 111 and 240 patients underwent sublobar resection and lobectomy, respectively). Presence of pathological necrosis was identified in 32 patients (9%). Presence of pathological necrosis was significantly associated with sex, smoking, clinical T classification in the 8[th] edition and pathological tumor size (p<0.01, p<0.001, p<0.01, p<0.001, respectively). Presence of pathological necrosis correlated with an increased risk of recurrence, compared with those without pathological necrosis (5-year RFP, 70.5%vs 93.8%; p<0.001). Presence of pathological necrosis did not affect OS (5-year OS, 80.8%vs 92.3%; p=0.21).Figure 1



      Conclusion:
      In patients with small lung adenocarcinoma ≦2cm, presence of pathological necrosis was significantly associated with increased risk of recurrence.

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    YI 01 - Young Investigator and First Time Attendee Session (ID 588)

    • Event: WCLC 2017
    • Type: Young Investigator
    • Track: Education/Publication/Career Development
    • Presentations: 1
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      YI 01.11 - The Young Investigator Travel Award Experience - A Report from a Previous Award Winner (ID 7854)

      08:00 - 11:30  |  Presenting Author(s): Takahiro Karasaki

      • Abstract
      • Presentation
      • Slides

      Abstract:
      I received the WCLC 2016 Young Investigator Travel Award for my presentation entitled “Immunogram for cancer-immunity cycle towards personalized immunotherapy of lung cancer”. It was my great honor to receive the award, and I want to thank the conference committee and all the conference attendees. This was my first time to attend the WCLC, and I enjoyed the conference and my stay in Vienna. I was given the opportunity to join the Faculty Dinner held in Vienna City Hall. It was a fabulous experience, and I thoroughly enjoyed sitting at the same table as world-renowned surgeons and oncologists. During the conference, I mainly attended immunotherapy sessions where I learned about the results of the most recent clinical studies. Furthermore, while attending the biomarker session, I realized that biomarkers in this field are still inadequate and the development of useful biomarkers in immunotherapy is an urgent need. Receiving the young investigator scholarship has encouraged me to continue our efforts to unveil the tumor microenvironment in each patient using individual next-generation sequencing data in order to develop “next-generation biomarkers” and achieve optimal personalized immunotherapy. Last year, in a Perspectives article in Science, Blank et al. proposed the concept of the cancer immunogram, a framework to illustrate multiple parameters that influence the cancer-immunity interaction (1). In their article, the concept was applied theoretically to patients but not tested in practice. To accomplish this, we developed an immunogram reflecting the cancer immunity cycle using next-generation sequencing data, and applied it to real patients with lung cancer. An immunogram for the cancer immunity cycle is a radar chart that consists of eight molecular profiles relevant to the development of T-cell immunity to tumor cells. We sought to translate cumbersome omics data into easily comprehensible “report cards” for clinicians. Immunograms can be used as integrated biomarkers, and may become a valuable resource for optimal personalized immunotherapy. After the presentation at the WCLC 2016, our findings were published in the Journal of Thoracic Oncology in May (2). It was an honor that our article was chosen by the Editor to be a featured article and was introduced by an elegant review (3). We recently updated our method by normalizing the immunogram score using TCGA data. We are pleased to share the details of this improvement during the present conference. Although we are working in a challenging field and there is still a long way to go, we are encouraged by the award and will continue to struggle toward further breakthroughs.  References (1) Blank CU, Haanen JB, Ribas A, Schumacher TN. Cancer immunology. The “cancer immunogram” Science. 2016;352:658-60. (2) Karasaki T, Nagayama K, Kuwano H, et al. An Immunogram for the Cancer-Immunity Cycle: Towards Personalized Immunotherapy of Lung Cancer. J Thorac Oncol.2017;12(5):791-803. (3) Botling J, Sandelin M. Immune Biomarkers on the Radar-Comprehensive "Immunograms" for Multimodal Treatment Prediction. J Thorac Oncol.2017;12(5):770-2.

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