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

2020 Fiscal Year Final Research Report

• 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
• Keywords: 膵臓癌 / マウスモデル / 免疫療法

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.

Free Research Field

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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。