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The significance of macrophages in anti-cancer immune responses

Research Project

Project/Area Number 20H03459
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49020:Human pathology-related
Research InstitutionKumamoto University

Principal Investigator

komohara Yoshihro  熊本大学, 大学院生命科学研究部(医), 教授 (40449921)

Co-Investigator(Kenkyū-buntansha) 浅野 謙一  東京薬科大学, 生命科学部, 准教授 (10513400)
藤原 章雄  熊本大学, 大学院生命科学研究部(医), 准教授 (70452886)
大西 紘二  熊本大学, 大学院生命科学研究部(医), 特任准教授 (40613378)
Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2023: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Keywordsマクロファージ / 病理学
Outline of Research at the Start

一般的にがん・悪性腫瘍の微小環境には免疫細胞や線維芽細胞、血管内皮細胞など多数の宿主由来細胞が存在する。本研究では、微小環境における免疫細胞、主にマクロファージに注目し免疫抑制に関わるメカニズムを探索していく。

Outline of Final Research Achievements

The role of macrophages in various cancers was clarified. Through organ-transversal studies, it was revealed that tumor-associated macrophages act suppressively against cancer immunity. On the other hand, macrophages present in the lymph nodes were suggested to have a role in activating cancer immunity as antigen-presenting cells. The identification of compounds that induce the activation of both tumor-associated macrophages and lymph node sinus macrophages was also conducted, and their anti-tumor effects were demonstrated through animal experiments (preclinical trials).

Academic Significance and Societal Importance of the Research Achievements

様々な癌腫におけるマクロファージの役割を明らかにした。臓器横断的な研究により、腫瘍関連マクロファージががん免疫に対して抑制的に働くことを明らかにした。一方で、リンパ節に存在するマクロファージは抗原提示細胞として、がん免疫を賦活化させる役割があることが示唆された。腫瘍関連マクロファージとリンパ節洞マクロファージそれぞれの活性化を誘導する化合物の同定も行い、動物実験(前臨床試験により)、それらの抗腫瘍効果を実証した。以上の成果は、新たながん免疫に関わる創薬につながる結果である。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • Research Products

    (25 results)

All 2023 2022 2021 2020 Other

All Journal Article (18 results) (of which Peer Reviewed: 18 results,  Open Access: 12 results) Presentation (5 results) (of which Invited: 5 results) Remarks (2 results)

  • [Journal Article] The Significance of SPP1 in Lung Cancers and Its Impact as a Marker for Protumor Tumor-Associated Macrophages2023

    • Author(s)
      Matsubara Eri、Yano Hiromu、Pan Cheng、Komohara Yoshihiro、Fujiwara Yukio、Zhao Shukang、Shinchi Yusuke、Kurotaki Daisuke、Suzuki Makoto
    • Journal Title

      Cancers

      Volume: 15 Issue: 8 Pages: 2250-2250

    • DOI

      10.3390/cancers15082250

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intravital imaging of immune responses in intestinal inflammation2023

    • Author(s)
      Honda Masaki、Kadohisa Masashi、Yoshii Daiki、Komohara Yoshihiro、Hibi Taizo
    • Journal Title

      Inflammation and Regeneration

      Volume: 43 Issue: 1 Pages: 9-9

    • DOI

      10.1186/s41232-023-00262-w

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Involvement of protumor macrophages in breast cancer progression and characterization of macrophage phenotypes2023

    • Author(s)
      Komohara Y.#, Kurotaki D.#, Tsukamoto H.#, Miyasato Y., Yano H., Pan C., Yamamoto Y., and Fujiwara Y. (#Contributed equally)
    • Journal Title

      Cancer Sci.

      Volume: - Issue: 6 Pages: 2220-2229

    • DOI

      10.1111/cas.15751

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Dysfunction of sinus macrophages in tumor‐bearing host induces resistance to immunotherapy2023

    • Author(s)
      Anami Toshiki、Pan Cheng、Fujiwara Yukio、Komohara Yoshihiro、Yano Hiromu、Saito Yoichi、Sugimoto Masamichi、Wakita Daiko、Motoshima Takanobu、Murakami Yoji、Yatsuda Junji、Takahashi Naofumi、Suzu Shinya、Asano Kenichi、Tamada Koji、Kamba Tomomi
    • Journal Title

      Cancer Science

      Volume: 115 Issue: 1 Pages: 59-69

    • DOI

      10.1111/cas.16003

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression of macrophage/dendritic cell related molecules in lymph node sinus macrophages2023

    • Author(s)
      Yamada Rin、Ohnishi Koji、Pan Cheng、Yano Hiromu、Fujiwara Yukio、Shiota Takuya、Mikami Yoshiki、Komohara Yoshihiro
    • Journal Title

      Microbiology and Immunology

      Volume: 67 Issue: 11 Pages: 490-500

    • DOI

      10.1111/1348-0421.13095

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Fusobacterium nucleatum promotes esophageal squamous cell carcinoma progression via the NOD1/RIPK2/NF-κB pathway2022

    • Author(s)
      Nomoto Daichi、Baba Yoshifumi、Liu Yang、Tsutsuki Hiroyasu、Okadome Kazuo、Harada Kazuto、Ishimoto Takatsugu、Iwatsuki Masaaki、Iwagami Shiro、Miyamoto Yuji、Yoshida Naoya、Watanabe Masayuki、Moroishi Toshiro、Komohara Yoshihiro、Sawa Tomohiro、Baba Hideo
    • Journal Title

      Cancer Letters

      Volume: 530 Pages: 59-67

    • DOI

      10.1016/j.canlet.2022.01.014

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Blocking cholesterol efflux mechanism is a potential target for antilymphoma therapy2022

    • Author(s)
      Yano Hiromu、Fujiwara Yukio、Horlad Hasita、Pan Chang、Kai Keitaro、Niino Daisuke、Ohsawa Kumiko、Higashi Morihiro、Nosaka Kisato、Okuno Yutaka、Tamaru Jun‐ichi、Mukasa Akitake、Matsuoka Masao、Komohara Yoshihiro
    • Journal Title

      Cancer Science

      Volume: 113 Issue: 6 Pages: 2129-2143

    • DOI

      10.1111/cas.15349

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] M-CSFR expression in the embryonal component of hepatoblastoma and cell-to-cell interaction between macrophages and hepatoblastoma2022

    • Author(s)
      Li Lianbo、Irie Tomoaki、Yoshii Daiki、Komohara Yoshihiro、Fujiwara Yukio、Esumi Shigeyuki、Kadohisa Masashi、Honda Masaki、Suzu Shinya、Matsuura Toshiharu、Kohashi Kenichi、Oda Yoshinao、Hibi Taizo
    • Journal Title

      Medical Molecular Morphology

      Volume: 55 Issue: 3 Pages: 236-247

    • DOI

      10.1007/s00795-022-00323-y

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Classification of <scp>PD‐L1</scp> expression in various cancers and macrophages based on immunohistocytological analysis2022

    • Author(s)
      Saito Yoichi、Fujiwara Yukio、Shinchi Yusuke、Mito Remi、Miura Yuji、Yamaguchi Tomoya、Ikeda Koei、Urakami Shinji、Nakashima Yuta、Sakagami Takuro、Suzuki Makoto、Tabata Yasuhiko、Komohara Yoshihiro
    • Journal Title

      Cancer Science

      Volume: 113 Issue: 9 Pages: 3255-3266

    • DOI

      10.1111/cas.15442

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] IL-34 in hepatoblastoma cells potentially promote tumor progression via autocrine and paracrine mechanisms2022

    • Author(s)
      Irie T, Yoshii D, Komohara Y, Fujiwara Y, Kadohisa M, Honda M, Suzu S, Matsuura T, Kohashi K, Oda Y, Hibi T
    • Journal Title

      Cancer Med

      Volume: 11 Issue: 6 Pages: 1441-1453

    • DOI

      10.1002/cam4.4537

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] SPP1 Derived from Macrophages Is Associated with a Worse Clinical Course and Chemo-Resistance in Lung Adenocarcinoma2022

    • Author(s)
      Matsubara Eri、Komohara Yoshihiro、Esumi Shigeyuki、Shinchi Yusuke、Ishizuka Shiho、Mito Remi、Pan Cheng、Yano Hiromu、Kobayashi Daiki、Fujiwara Yukio、Ikeda Koei、Sakagami Takuro、Suzuki Makoto
    • Journal Title

      Cancers

      Volume: 14 Issue: 18 Pages: 4374-4374

    • DOI

      10.3390/cancers14184374

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SOX9 contributes to the progression of ductular reaction for the protection from chronic liver injury2022

    • Author(s)
      Yoshii Daiki、Shimata Keita、Yokouchi Yuji、Komohara Yoshihiro、Suda Hiroko、Honda Masaki、Yamamura Kenichi、Hibi Taizo、Inomata Yukihiro
    • Journal Title

      Human Cell

      Volume: 35 Issue: 2 Pages: 721-734

    • DOI

      10.1007/s13577-022-00683-8

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The expression of PD-1 ligand 1 on macrophages and its clinical impacts and mechanisms in lung adenocarcinoma2022

    • Author(s)
      Shinchi Yusuke、Ishizuka Shiho、Komohara Yoshihiro、Matsubara Eri、Mito Remi、Pan Cheng、Yoshii Daiki、Yonemitsu Kimihiro、Fujiwara Yukio、Ikeda Koei、Tamada Koji、Sakagami Takuro、Suzuki Makoto
    • Journal Title

      Cancer Immunology, Immunotherapy

      Volume: 71 Issue: 11 Pages: 2645-2661

    • DOI

      10.1007/s00262-022-03187-4

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High T-cell infiltration in tumor tissue and younger age predict the response to pembrolizumab in recurrent urothelial cancer.2021

    • Author(s)
      Anami T, Komohara Y (**), Miura Y, Yamanaka K, Kurahashi R, Segawa T, Motoshima T, Murakami Y, Yatsuda J, Yamaguchi T, Sugiyama Y, Jinnouchi Y, Kamba T.
    • Journal Title

      Med Mol Morphol. 54:316-323, 2021.

      Volume: 54

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] α1-acid glycoprotein enhances the immunosuppressive and protumor functions of tumor-associated macrophages.2021

    • Author(s)
      Matsusaka K, Fujiwara Y, Pan C, Esumi S, Saito Y, Bi J, Nakamura Y, Mukunoki A, Takeo T, Nakagata N, Yoshii D, Fukuda R, Nagasaki T, Tanaka R, Komori H, Maeda H, Watanabe H, Tamada K, Komohara Y (**), Maruyama T.
    • Journal Title

      Cancer Res. 81:4545-4559, 2021

      Volume: 81 Pages: 4545-4559

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CD169 expression on lymph node macrophages predicts in patients with gastric cancer.2021

    • Author(s)
      Kumamoto K, Tasaki T, Ohnishi K, Shibata M, Shimajiri S, Harada M, Komohara Y (**), Nakayama T.
    • Journal Title

      Front Oncol. 11:636751, 2021

      Volume: 11 Pages: 636751-636751

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Flavonoid Compounds Contained in Epimedii Herba Inhibit Tumor Progression by Suppressing STAT3 Activation in the Tumor Microenvironment.2020

    • Author(s)
      Pan C, Fujiwara Y, Horlad H, Shiraishi D, Iriki T, Tsuboki J, Ikeda T, Komohara Y
    • Journal Title

      Front Pharmacol. 11:262, 2020

      Volume: 11 Pages: 262-262

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] CD163 deficiency facilitates LPS-induced inflammatory responses and endotoxin shock in mice.2020

    • Author(s)
      Fujiwara Y, Ohnishi K, Horlad H, Sato Y, Shiraishi D, Takeya H, Yoshii D, Kaieda S, Hoshino T, Komohara Y
    • Journal Title

      Clin Transl Immunol 9; e1162, 2020.

      Volume: 9 Pages: 1162-1162

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] がん免疫における免疫応答とリンパ節マクロファージ2023

    • Author(s)
      菰原義弘
    • Organizer
      第112回日本病理学会総会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] がん微小環境におけるマクロファージの役割2022

    • Author(s)
      菰原義弘
    • Organizer
      第111回日本病理学会総会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] リンパ洞に存在するマクロファージはがん免疫に関与している2022

    • Author(s)
      菰原義弘
    • Organizer
      第81回 日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] がん免疫におけるマクロファージの重要性と新たな治療戦略2022

    • Author(s)
      菰原義弘
    • Organizer
      第50回日本臨床免疫学会総会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] がん免疫微小環境におけるマクロファージの重要性2021

    • Author(s)
      菰原義弘
    • Organizer
      第109回日本病理学会総会@東京
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Remarks] 熊本大学細胞病理学ホームページ

    • URL

      https://www.kumamoto-pathology1.jp/

    • Related Report
      2023 Annual Research Report
  • [Remarks] 細胞病理学講座

    • URL

      https://www.kumamoto-pathology1.jp/

    • Related Report
      2022 Annual Research Report

URL: 

Published: 2020-04-28   Modified: 2025-01-30  

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