Virtual Library

 x 
My Library Virtual Library FAQ

Start Your Search

S. Koyama



Author of

  • +

    P2.07 - Immunology and Immunotherapy (ID 708)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Immunology and Immunotherapy
    • Presentations: 1
    • +

      P2.07-009 - Monitoring Nivolumab Binding as a Method to Clarify the Residual Therapeutic Effects in Previously Treated Lung Cancer Patients (ID 8098)

      09:30 - 09:30  |  Author(s): S. Koyama

      • Abstract
      • Slides

      Background:
      Although the biological durability of Nivolumab, the PD-1 blocking antibody, was reported to continue longer than 12 weeks, the maximum duration of its efficacy, along with toxicity, after discontinuation and the correlation between residual binding and clinical events in cases of sequential therapeutic regimens remain unclear.

      Method:
      Peripheral blood, pleural effusion and bronchoalveolar lavage fluid were obtained from non-small cell lung cancer patients previously treated with Nivolumab. To evaluate the efficacy of the treatment, we developed a simple technique to identify Nivolumab binding status — complete binding, partial binding and no binding — in T cells from patient samples using flowcytometry, which can also be used to obtain T cell differentiation markers and transcriptome profiles, particularly in the Nivolumab bound T cell population. Based on this method, we tracked the binding status in T cells primarily from peripheral blood in patients who received a sequential therapeutic regimen after Nivolumab treatment.

      Result:
      While the decrease in frequency of Nivolumab binding after discontinuation was observed in all cases where long term monitoring was possible, Nivolumab binding in T cells from peripheral blood was detected until more than 20 weeks, though effective binding could have ceased before that time point. We found that the direct effects on Nivolumab binding via sequential treatment were limited. Finally, we observed in clinical cases that our monitoring technique was also helpful in understanding the cause of clinical events and its residual efficacy in patients who previously received Nivolumab.

      Conclusion:
      Monitoring of Nivolumab binding to T cells after discontinuation can be valuable when planning sequential therapeutic regimens in the following ways: estimating the potential residual efficacy, predicting the risk of immune-related adverse events and the time of relapse due to complete loss of efficacy, and investigating the changes in the immune profile in Nivolumab bound T cells.

      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.

  • +

    P3.02 - Biology/Pathology (ID 620)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
    • +

      P3.02-023 - Semaphorin 7A Reduces Response to EGFR-TKI Treatment via Apoptosis in Human Lung Adenocarcinoma (ID 8074)

      09:30 - 09:30  |  Author(s): S. Koyama

      • Abstract

      Background:
      Most patients harboring epidermal growth factor receptor (EGFR) mutations experience relapse to EGFR-Tyrosin kinase inhibitors (TKI). So it is necessary to overcome the resistance to EGFR-TKI. We found that Semaphorin 7A (SEMA7A) is upregulated by EGFR signals. The role of SEMA7A in human lung adenocarcinoma is unknown, so we annlyzed the function of SEMA7A in human lung adenocarinoma.

      Method:
      We compared transcriptomes of NIH3T3 cell lines overexpressing wild type (WT) EGFR with Next, we investigated which pathways regulated the expression of SEMA7A in human lung adenocarcinoma cell line. Furthermore, we investigated the expression of SEMA7A by immunohistochemistry (IHC), and the correlation of SEMA7A and phosphorylation S6 (pS6) in 129 lung adenocarcinoma patients were analyzed. We also investigated the correlation of SEMA7A expression with the prognosis or drug response in 44 stage IV lung adenocarcinoma patients. Finally, we investigated the efficacy of EGFR-TKI in SEMA7A WT and KO (by CRISPR/CAS9) in vitro and in vivo.

      Result:
      The expression of SEMA7A was regulated by EGFR signals. Furthermore, the expression of SEMA7A was downregulated by mTOR signals in human lung adenocarinoma cells and clinical samples. High SEMA7A lung cancers tended to get EGFR-TKI resistance, in vivo, in vitro via apoptosis. In clinical samples, high SEMA7A expression tumor tended to get EGFR-TKI resistance.

      Conclusion:
      We revealed that the SEMA7A regulated the efficacy to EGFR-TKI via apoptosis.