Development of novel immunotherapy by elucidation of host immune response in pancreatic adenocarcinoma of mouse model

• Project/Area Number: 18K07935
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Department of Clinical Research, National Hospital Organization Kanazawa Medical Center (2019-2020); Kanazawa University (2018)
• Principal Investigator: Komura Takuya 独立行政法人国立病院機構(金沢医療センター臨床研究部), その他部局等, 研究員 (90623322)
• Co-Investigator(Kenkyū-buntansha): 酒井 佳夫 金沢大学, 医学系, 准教授 (80401925)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 膵臓癌 / マウスモデル / 免疫療法 / 免疫状態

Outline of Final Research Achievements

I established mouse pancreatic cancer peritoneal dissemination model and liver metastasis model that are close to the actual clinical picture. I analyzed changes in the host immune response during pancreatic cancer chemotherapy with Gemcitabine. Immunomodification targeting Gr1+ CD11+ bone marrow-derived immunosuppressive cells (MDSC) enhances the therapeutic effect on Gemcitabine. Furthermore, cytotoxic CD8 + T cell activation was observed in Gemcitabine treatment, and Th1 helper T cells and M1 macrophages were induced by the combined treatment of anti-PD-1 antibody targeting PD-1, which is an immune checkpoint molecule. This treatment was found to enhance the antitumor effect.

Academic Significance and Societal Importance of the Research Achievements

膵臓癌に関する免疫治療において有望なものが開発されていないのが現状であった。膵臓癌特有の宿主免疫応答および線維化に富んだ腫瘍局所の免疫状態に対する研究が十分でないことが大きな要因と考えており、これらの宿主免疫状態を解明できた。本研究の成果が、今後の膵臓癌に対する新たな免疫治療を加えた化学療法開発においてブレークスルーとなる可能性がある。

Research Products

• [Journal Article] Combination of gemcitabine and anti-PD-1 antibody enhances the anticancer effect of M1 macrophages and the Th1 response in a murine model of pancreatic cancer liver metastasis (2020)
  • Author(s): Ho Tuyen Thuy Bich、Nasti Alessandro、Seki Akihiro、Komura Takuya、Inui Hiiro、Kozaka Takashi、Kitamura Yoji、Shiba Kazuhiro、Yamashita Taro、Yamashita Tatsuya、Mizukoshi Eishiro、Kawaguchi Kazunori、Wada Takashi、Honda Masao、Kaneko Shuichi、Sakai Yoshio
  • Journal Title: Journal for ImmunoTherapy of Cancer Volume: 8 Issue: 2 Pages: e001367-e001367
  • DOI: 10.1136/jitc-2020-001367
  • NAID: 120007185659
  • Peer Reviewed / Open Access
• [Presentation] 膵臓癌マウスモデルにおけるGemcitabine治療が引き起こす宿主免疫応答の変化 (2018)
  • Author(s): 小村卓也、酒井佳夫、高畠央、吉田佳子、奥薗舞、ナスティ・アレッサンドロ、山田長司、金子周一
  • Organizer: 日本膵臓学会