Project/Area Number |
18K08616
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 55020:Digestive surgery-related
|
Research Institution | Osaka University |
Principal Investigator |
MAKINO TOMOKI 大阪大学, 医学系研究科, 助教 (80528620)
|
Project Period (FY) |
2018-04-01 – 2021-03-31
|
Project Status |
Completed (Fiscal Year 2020)
|
Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
|
Keywords | 食道癌 / 複合療法 / 化学療法 / 免疫療法 / バイオマーカー / 免疫チェックポイント阻害剤 / 腫瘍浸潤リンパ球 / PD-L1 / CD8 / リンパ球 / 併用療法 / 免疫チェックポイント阻害薬 / 腫瘍浸潤T細胞 / 免疫微小環境 / 胃癌 |
Outline of Final Research Achievements |
Tumor PD-L1 expression was higher in esophageal cancer patients with preoperative chemotherapy (NAC) compared with patients without NAC, and the number of tumor-infiltrating CD8 + cells was lower in PD-L1-positive tumors, implying that NAC may induce tumor PD-L1 expression and somehow contribute to treatment resistance. In advanced cases, the prognosis was significantly better in cases with larger number of CD3 + / CD8 + cells (immunoscore) infiltrating to the central and marginal areas of the tumor. In addition, the prognosis of the CD3 high group was better than CD3 low group in pretherapeutic endoscopic biopsies, and the number of CD3 + / CD8 + cells was higher in responders to NAC. Meanwhile, as the first-line treatment as a clinical trial, we administered chemotherapy plus Nivolumab to 13 patients with advanced / recurrent esophageal cancer at our hospital, and obtained favorable treatment outcomes. We next plan to analyze clinical samples of these cases.
|
Academic Significance and Societal Importance of the Research Achievements |
本研究では食道癌切除標本および内視鏡生検検体を用いて腫瘍PD-L1発現や腫瘍内浸潤T細胞数(TILs)を中心としたがん免疫微小環境と化学療法との相互作用を明らかにした。また、実臨床においても進行・再発食道癌に対する1次治療(治験)としての化療+Nivoluma治療の有用性を確認しており、今後これらの臨床検体を解析することで化療+Nivolumaの治療効果予測・予後マーカー開発につながる可能性がある。そうなれば食道癌の個別化治療の確立に大きく貢献し、最終的に飛躍的な治療成績の向上および医療費軽減につながり社会的意義も甚大と考える。
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