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Development of novel cancer immunotherapeutic approach based on age-associated inflammatory response

Research Project

Project/Area Number 18K07325
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionKumamoto University

Principal Investigator

Tsukamoto Hirotake  熊本大学, 大学院生命科学研究部(医), 講師 (10433020)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
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)
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
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).

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。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (21 results)

All 2021 2020 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (12 results) (of which Peer Reviewed: 12 results,  Open Access: 10 results) Presentation (4 results) (of which Invited: 2 results) Book (4 results)

  • [Int'l Joint Research] Roswell Park Comprehensive Cancer Center/Department of Surgical Oncology/Center for Immunotherapy(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] The role of macrophages in anti-tumor immune responses: pathological significance and potential as therapeutic targets.2021

    • Author(s)
      Tsukamoto H., Komohara Y. and Oshiumi H
    • Journal Title

      Human Cell

      Volume: -

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [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.
    • Journal Title

      Mol. Ther. Methods Clin. Dev.

      Volume: -

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [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.
    • Journal Title

      Int J Mol Sci .

      Volume: 22(4) Issue: 4 Pages: 1958-1958

    • DOI

      10.3390/ijms22041958

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aging-Associated Extracellular Vesicles Contain Immune Regulatory microRNAs Alleviating Hyperinflammatory State and Immune Dysfunction in the Elderly2020

    • Author(s)
      Hirotake Tsukamoto, Takahisa Kouwaki, Hiroyuki Oshiumi
    • Journal Title

      iScience

      Volume: 23 Issue: 9 Pages: 101520-101520

    • DOI

      10.1016/j.isci.2020.101520

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [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.
    • Journal Title

      Oncoimmunology

      Volume: 9(1) Issue: 1 Pages: 1814620-1814620

    • DOI

      10.1080/2162402x.2020.1814620

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HTLV-1 induces T cell malignancy and inflammation by viral antisense factor-mediated modulation of the cytokine signaling2020

    • Author(s)
      Higuchi Yusuke、Yasunaga Jun-ichirou、Mitagami Yu、Tsukamoto Hirotake、Nakashima Kazutaka、Ohshima Koichi、Matsuoka Masao
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 117 Issue: 24 Pages: 13740-13749

    • DOI

      10.1073/pnas.1922884117

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Induced pluripotent stem cell‐derived myeloid cells expressing OX40 ligand amplify antigen‐specific T cells in advanced melanoma2020

    • Author(s)
      Kimura Toshihiro、Fukushima Satoshi、Okada Etsuko、Miyashita Azusa、Tsukamoto Hirotake、Uemura Yasushi、Senju Satoru、Ihn Hironobu
    • Journal Title

      Pigment Cell & Melanoma Research

      Volume: - Issue: 5 Pages: 744-755

    • DOI

      10.1111/pcmr.12887

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cancer therapy with MHC-deficient and interferon β-producing myeloid cells derived from allogeneic embryonic stem cells.2019

    • Author(s)
      Satoshi Umemoto, Miwa Haruta, Masataka Sakisaka, Tokunori Ikeda, Hirotake Tsukamoto, Yoshihiro Komohara, Motohiro Takeya, Yasuharu Nishimura, Satoru Senju.
    • Journal Title

      Cancer Science

      Volume: 110 Pages: 3027-3037

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nivolumab‐induced colitis in a patient with malignant melanoma: A case report and immunological analysis2019

    • Author(s)
      Miyashita Azusa、Fukushima Satoshi、Tsukamoto Hirotake、Itai Hisae、Miyamoto Hideaki、Nakahara Satoshi、Kubo Yosuke、Kimura Toshihiro、Kuriyama Haruka、Ihn Hironobu
    • Journal Title

      The Journal of Dermatology

      Volume: 0000 Issue: 9 Pages: 0000-0000

    • DOI

      10.1111/1346-8138.14857

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combined Blockade of IL6 and PD-1/PD-L1 Signaling Abrogates Mutual Regulation of Their Immunosuppressive Effects in the Tumor Microenvironment2018

    • Author(s)
      Tsukamoto Hirotake、Fujieda Koji、Miyashita Azusa、Fukushima Satoshi、Ikeda Tokunori、Kubo Yosuke、Senju Satoru、Ihn Hironobu、Nishimura Yasuharu、Oshiumi Hiroyuki
    • Journal Title

      Cancer Research

      Volume: 78 Issue: 17 Pages: 5011-5022

    • DOI

      10.1158/0008-5472.can-18-0118

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activation of TLR3 and its adaptor TICAM-1 increases miR-21 levels in extracellular vesicles released from human cells2018

    • Author(s)
      Fukushima Yoshimi、Okamoto Masaaki、Ishikawa Kana、Kouwaki Takahisa、Tsukamoto Hirotake、Oshiumi Hiroyuki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: In Press Issue: 3 Pages: 744-750

    • DOI

      10.1016/j.bbrc.2018.04.146

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immune-suppressive effects of interleukin-6 on T-cell-mediated anti-tumor immunity2017

    • Author(s)
      Tsukamoto Hirotake、Fujieda Koji、Senju Satoru、Ikeda Tokunori、Oshiumi Hiroyuki、Nishimura Yasuharu
    • Journal Title

      Cancer Science

      Volume: 109 Issue: 3 Pages: 523-530

    • DOI

      10.1111/cas.13433

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Exosomal miR192 regulates inflammatory response induced by Influenza whole vaccine2019

    • Author(s)
      Hirotake Tsukamoto, Takahisa Kouwaki, Kana Ishikawa, and Hiroyuki Oshiumi
    • Organizer
      第48回 日本免疫学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Targeting of age-associated increase in IL-6 improves the responsiveness to cancer immunotherapies in old age2019

    • Author(s)
      Hirotake Tsukamoto
    • Organizer
      第78回 日本癌学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] Combined blockade of IL-6 and PD-1/PD-L1 signaling abrogates mutual regulation of their immunosuppressive effects in the tumor microenvironment2018

    • Author(s)
      Hirotake Tsukamoto, Azusa Miyashita, Satoshi Fukushima, Yasuharu Nishimura, Hiroyuki Oshiumi.
    • Organizer
      第47回 日本免疫学会学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] Combined blockade of IL-6 and PD-1/PD-L1 signals breaks mutual regulation of their immunosuppressive effects2018

    • Author(s)
      Hirotake Tsukamoto
    • Organizer
      第77回 日本癌学会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Book] Precision Medicine がん治療における個別化医療の潮流2020

    • Author(s)
      塚本博丈
    • Total Pages
      8
    • Publisher
      北隆館
    • Related Report
      2020 Annual Research Report
  • [Book] 実験医学増刊「新・腫瘍免疫学: がん免疫におけるマクロファージの役割」2020

    • Author(s)
      菰原 義弘, 塚本 博丈
    • Total Pages
      6
    • Publisher
      羊土社
    • Related Report
      2020 Annual Research Report
  • [Book] 「がん免疫におけるマクロファージの役割」 実験医学増刊2019

    • Author(s)
      菰原義弘、塚本博丈
    • Total Pages
      9
    • Publisher
      羊土社
    • Related Report
      2019 Research-status Report
  • [Book] IL-6とPD-1/PD-L1シグナルの併用阻害による免疫抑制効果の相互制御の遮断2019

    • Author(s)
      塚本博丈、押海裕之
    • Total Pages
      6
    • Publisher
      臨床免疫・アレルギー科 科学評論社
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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