Development of novel cancer immunotherapeutic approach based on age-associated inflammatory response
| Project/Area Number |
18K07325
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | がん免疫療法 / 炎症 / 免疫老化 / マクロファージ / T細胞 / PD-1阻害療法 / がん / 加齢 / 免疫応答 / 細胞老化 / IL-6 / 老化 / Th１細胞 / 免疫抑制 / 自己炎症応答 |
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| Outline of Final Research Achievements |
We have been working on the research based on the hypothesis that "age-related immunological changes affect the effectiveness of cancer immunotherapy," and proposed the possibility that the immune enhancing efficacy of anti-PD-1 therapy is augmented by combined depletion of macrophages that are responsible for the inflammatory response (Tsukamoto H. et al., Cancer Res. 2018). Furthermore, we performed the analysis regarding the effect of macrophages on the inflammatory response in aged animals, and found that inflammation augmented in aged animals was due to the qualitative changes of macrophages associated with organism aging and enhancement of their inflammatory response (Tsukamoto H. et al., IScience 2020).
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| Academic Significance and Societal Importance of the Research Achievements |
「個体老化に伴う免疫機能の変化」に着目して老齢マウスを用いた本研究は、「老化」と「がんに対する免疫応答」という研究分野を融合させて担がん個体の免疫応答を捉える、という他に類を見ない観点からの研究である一方、がん免疫療法の対象の多くが高齢者である、という我が国の現状に即した研究成果として、高齢がん患者におけるがん免疫療法の感受性の改善、加齢に伴う免疫機能低下を制御する上でも基盤的知見を提供するはずである。そして、これらの成果は現在行っている、ヒトを対象とした前臨床研究のきっかけとなっており、本研究にて提案されたがん免疫療法の増強戦略はさらなる臨床応用への発展が期待できる。
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Report
(4 results)
Research Products
(21 results)
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[Journal Article] Improved safety of induced pluripotent stem cell-derived antigen presenting cell-based cancer immunotherapy.2021
Author(s)
ashima H., Zhang R., Kobayashi T., Hagiya Y., Tsukamoto H., Liu T., Iwama T., Nakatsuka R., Mishima Y., Okada S., Senju S., Takasu N., Kaneko S., Idiris A., Ohdan H., Nakatsura T., Uemura Y.
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Journal Title
Mol. Ther. Methods Clin. Dev.
Volume: -
Related Report
Peer Reviewed
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[Journal Article] Immunotherapy with 4-1BBL-Expressing iPS Cell-Derived Myeloid Lines Amplifies Antigen-Specific T Cell Infiltration in Advanced Melanoma2021
Author(s)
Kuriyama H, Fukushima S, Kimura T, Kanemaru H, Miyashita A, Okada E, Kubo Y, Nakahara S, Tokuzumi A, Nishimura Y, Kajihara I, Makino K, Aoi J, Masuguchi S, Tsukamoto H, Inozume T, Zhang R, Nakatsura T, Uemura Y, Senju S, Ihn H.
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Journal Title
Int J Mol Sci .
Volume: 22(4)
Issue: 4
Pages: 1958-1958
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Generation of GM-CSF-producing antigen-presenting cells that induce a cytotoxic T cell-mediated antitumor response.2020
Author(s)
Mashima H, Zhang R, Kobayashi T, Hagiya Y, Tsukamoto H, Liu T, Iwama T, Yamamoto M, Lin C, Nakatsuka R, Mishima Y, Watanabe N, Yamada T, Senju S, Kaneko S, Idiris A, Nakatsura T, Ohdan H, Uemura Y.
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Journal Title
Oncoimmunology
Volume: 9(1)
Issue: 1
Pages: 1814620-1814620
DOI
Related Report
Peer Reviewed / Open Access
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