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The relationships of tumor micro environment and radiation resistance with clonal hematopoiesis

Research Project

Project/Area Number 20K16824
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52040:Radiological sciences-related
Research InstitutionOsaka University

Principal Investigator

Tatekawa Shotaro  大阪大学, 大学院医学系研究科, 特任助教(常勤) (40816550)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords放射線治療学 / 放射線治療抵抗性 / 腫瘍微小環境 / DNA変異解析 / clonal hematopoiesis / Clonal Hematopoiesis
Outline of Research at the Start

Clonal Hematopoiesis (CH) とは血液学的異常が無い人に血液細胞の体細胞クローンの増殖を認めることと定義され、一般的に加齢とともに頻度が増加することが知られている。これまでの報告より、CH が局所の炎症を惹起し腫瘍環境の変化に関わっている可能性が考えられる。一方、慢性炎症や血管新生を始めとする腫瘍微小環境の放射線治療抵抗性へ果たす役割は大きい。しかし、腫瘍微小環境が感受性に直接影響する放射線治療と、CH との関連については未だ不明である。それを解明し、放射線治療抵抗性 に対する新たな治療標的を模索するのが本研究の目的である。

Outline of Final Research Achievements

The current study aimed to elucidate the mechanism of clonal hematopoiesis(CH) and radiotherapy resistance. Sequence analysis of 67 patients with head and neck cancer showed that the presence of CH was a risk factor for both recurrence-free survival and local recurrence rate, as indicated by multivariate analysis including age and stage of disease. In addition, RNA-seq was performed in peripheral blood mononuclear cells with and without CH to compare gene expression, and the expression of genes that are major mediators of inflammation and immunity was higher in patients with CH. The possibility that the presence of CH may be involved in the induction of chronic inflammation was considered. Based on these results, we have created a mouse model of CH and are conducting additional analyses.

Academic Significance and Societal Importance of the Research Achievements

これまで放射線治療抵抗性へのアプローチとしては低酸素イメージングや線量増加などの報告が多いが、CH に伴う炎症の惹起や腫瘍微小環境の変化に着目した研究は皆無であった。本研究はその点において独自性があり、化学放射線治療を受ける頭頸部癌患者においてCH の有無が局所再発率に関与していることが判明した。今後、CH による腫瘍微小環境の変化が放射線治療抵抗性へ関与していることをコンディショナルノックアウトマウスを用いて解析予定だが、それらが解明できれば抗炎症作用をもつ薬剤の投与や血管新生阻害剤、マクロファージの遊走を阻害する薬剤など、CH を有する患者における新たな治療戦略の設計が可能となる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (18 results)

All 2023 2022 2021

All Journal Article (12 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 12 results,  Open Access: 11 results) Presentation (6 results)

  • [Journal Article] Stereotactic ablative body radiotherapy with a central high dose using CyberKnife for metastatic lung tumors2023

    • Author(s)
      Hayashi Kazuhiko、Suzuki Osamu、Shiomi Hiroya、Ono Hitoshi、Setoguchi Akira、Nakai Masataka、Nakanishi Erina、Tatekawa Shotaro、Ose Naoko、Hirata Takero、Tamari Keisuke、Seo Yuji、Funaki Soichiro、Isohashi Fumiaki、Shimizu Shinichi、Shintani Yasushi、Ogawa Kazuhiko
    • Journal Title

      BMC Cancer

      Volume: 23 Issue: 1 Pages: 1-10

    • DOI

      10.1186/s12885-023-10635-6

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Establishment of a reference single-cell RNA sequencing dataset for human pancreatic adenocarcinoma2022

    • Author(s)
      Chijimatsu R、Kobayashi S、Takeda Y、Kitakaze M、Tatekawa S、Tachibana N、Saito T、Ennishi D、Tomida S、Sasaki K、Yamada D、Tomimaru Y、Takahashi H、Doki Y、Eguchi H
    • Journal Title

      iScience

      Volume: 25 Issue: 8 Pages: 104659-104659

    • DOI

      10.1016/j.isci.2022.104659

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] COVID-19 vaccine-induced Recurrence of the Radiation Recall Phenomenon in the Laryngeal Mucosa Due to a VEGF Inhibitor2022

    • Author(s)
      Tatekawa Shotaro、Hoshino Shigenori、Takemoto Norihiko、Oda Michio、Akino Yuichi、Iwahori Kota、Hirata Takero、Hayashi Kazuhiko、Tamari Keisuke、Seo Yuji、Isohashi Fumiaki、Shimizu Shinichi、Ogawa Kazuhiko
    • Journal Title

      Advances in Radiation Oncology

      Volume: 7 Issue: 6 Pages: 101048-101048

    • DOI

      10.1016/j.adro.2022.101048

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Radiation therapy enhances systemic antitumor efficacy in PD-L1 therapy regardless of sequence of radiation in murine osteosarcoma.2022

    • Author(s)
      Shohei Katsuki, Yutaka Takahashi, Keisuke Tamari, Kazumasa Minami, Wataru Takenaka, Yoriko Ibuki, Junya Yamamoto, Shotaro Tatekawa, Kazuhiko Hayashi, Yuji Seo, Fumiaki Isohashi, Kazuhiko Ogawa, Masahiko Koizumi
    • Journal Title

      PLoS ONE

      Volume: 17(7) Issue: 7 Pages: 0271205-0271205

    • DOI

      10.1371/journal.pone.0271205

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] N(6)-methyladenosine methylation-regulated polo-like kinase 1 cell cycle homeostasis as a potential target of radiotherapy in pancreatic adenocarcinoma2022

    • Author(s)
      Tatekawa Shotaro、Tamari Keisuke、Chijimatsu Ryota、Konno Masamitsu、Motooka Daisuke、Mitsufuji Suguru、Akita Hirofumi、Kobayashi Shogo、Murakumo Yoshiki、Doki Yuichiro、Eguchi Hidetoshi、Ishii Hideshi、Ogawa Kazuhiko
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 11074-11074

    • DOI

      10.1038/s41598-022-15196-5

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] High Dose Local Photon Irradiation Is Crucial in Anti-CTLA-4 Antibody Therapy to Enhance the Abscopal Response in a Murine Pancreatic Carcinoma Model.2022

    • Author(s)
      Junya Yamamoto, Yutaka Takahashi, Kazumasa Minami, Keisuke Tamari, Shohei Katsuki, Wataru Takenaka, Shotaro Tatekawa, Kazuhiko Hayashi, Yuji Seo, Fumiaki Isohashi, Kazuhiko Ogawa, Masahiko Koizumi.
    • Journal Title

      Cancers

      Volume: 14(9) Issue: 9 Pages: 2087-2087

    • DOI

      10.3390/cancers14092087

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Poly (ADP-ribose) polymerase inhibitors sensitize cancer cells to hypofractionated radiotherapy through altered selection of DNA double-strand break repair pathways2022

    • Author(s)
      Seo Y, Tamari K, Takahashi Y, Minami K, Tatekawa S, Isohashi F, Suzuki O, Akino Y, Ogawa K.
    • Journal Title

      International Journal of Radiation Biology

      Volume: in press Issue: 7 Pages: 1222-1234

    • DOI

      10.1080/09553002.2022.2020357

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Emerging roles of long noncoding and circular RNAs in pancreatic ductal adenocarcinoma.2022

    • Author(s)
      Sato, H., Hara, T., Tatekawa, S., Sasaki, K., Kobayashi, S., Kitagawa, T., Doki, Y., Eguchi, H., Ogawa, K., Uchida, S., Ishii, H.
    • Journal Title

      Front. Physiol.

      Volume: 13 Pages: 1025923-1025923

    • DOI

      10.3389/fphys.2022.1025923

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Poly (ADP-ribose) polymerase inhibitors sensitize cancer cells to hypofractionated radiotherapy through altered selection of DNA double-strand break repair pathways.2022

    • Author(s)
      Yuji Seo , Keisuke Tamari , Yutaka Takahashi , Kazumasa Minami , Shotaro Tatekawa , Fumiaki Isohashi , Osamu Suzuki , Yuichi Akino , Kazuhiko Ogawa
    • Journal Title

      International journal of radiation biology

      Volume: none Pages: 1-13

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Stereotactic Ablative Radiotherapy Using CyberKnife for Stage I Non-small-cell Lung Cancer: A Retrospective Analysis.2022

    • Author(s)
      Kazuhiko Hayashi , Osamu Suzuki , Hiroya Shiomi , Masataka Nakai , Kei Fujiwara , Erina Nakanishi , Shotaro Tatekawa , Takero Hirata , Keisuke Tamari , Haruhiko Hirata , Soichiro Funaki , Yuji Seo , Yoshito Takeda , Fumiaki Isohashi , Yasushi Shintani , Kazuhiko Ogawa
    • Journal Title

      Anticancer research

      Volume: 42 Issue: 1 Pages: 321-327

    • DOI

      10.21873/anticanres.15488

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Methylosystem for Cancer Sieging Strategy2021

    • Author(s)
      Tatekawa Shotaro、Ofusa Ken、Chijimatsu Ryota、Vecchione Andrea、Tamari Keisuke、Ogawa Kazuhiko、Ishii Hideshi
    • Journal Title

      Cancers

      Volume: 13 Issue: 20 Pages: 5088-5088

    • DOI

      10.3390/cancers13205088

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Monitoring expiratory carbon monoxide to study the effect of complete smoking cessation on definitive radiation therapy for early stage glottic carcinoma.2021

    • Author(s)
      Shotaro Tatekawa , Shigetoshi Shimamoto , Yoshiaki Miyata , Yutaro Yoshino , Takero Hirata , Keisuke Tamari , Yuji Seo , Fumiaki Isohashi , Yoshifumi Yamamoto , Atsuhiko Uno , Hidenori Inohara , Kazuhiko Ogawa
    • Journal Title

      Acta oncologica

      Volume: 60 Issue: 5 Pages: 582-588

    • DOI

      10.1080/0284186x.2020.1865563

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] m6Aにより制御されるPLK1の細胞周期恒常性は膵癌において新規放射線治療の標的となる2022

    • Author(s)
      立川章太郎 , 玉利慶介 , 千々松良太 , 光藤傑 , 秋田裕史 , 小林省吾 , 村雲芳樹 , 土岐祐一郎 , 江口英利 , 小川和彦 , 石井秀始
    • Organizer
      第81回 日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 抗CTLA-4抗体を使った免疫療法と放射線療法の併用治療は、膵管癌の局所のみならず遠隔巣においても抗腫瘍効果が得られる2021

    • Author(s)
      山本 純也 , 高橋 豊 , 皆巳 和賢 , 玉利 慶介 , 勝木 翔平 , 武中 渉 , 松谷 英樹 , 立川 章太郎 , 小川 和彦 , 小泉 雅彦
    • Organizer
      日本癌学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] マウス骨肉腫モデルに対する抗PD-L1抗体治療において治療順番に関わらず放射線治療は全身性の抗腫瘍効果を引き起こす2021

    • Author(s)
      勝木 翔平 , 高橋 豊 , 玉利 慶介 , 皆巳 和賢 , 武中 渉 , 山本 純也 , 松谷 英樹 , 立川 章太郎 , 小川 和彦 , 小泉 雅彦
    • Organizer
      日本癌学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 抗CTLA-4抗体併用下での放射線治療の線量増加による全身性抗腫瘍効果の増強について2021

    • Author(s)
      武中 渉 , 高橋 豊 , 皆巳 和賢 , 玉利 慶介 , 立川 章太郎 , 勝木 翔平 , 山本 純也 , 松谷 英樹 , 小泉 雅彦 , 小川 和彦
    • Organizer
      日本癌学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 松谷 英樹 , 玉利 慶介 , 立川 章太郎 , 皆巳 和賢 , 高橋 豊 , 武中 渉 , 勝木 翔平 , 山本 純也 , 小川 和彦 , 小泉 雅彦2021

    • Author(s)
      p16-HNSCC患者の血漿中cell-free DNAを用いたdigital-PCRによるHPV-DNA検出
    • Organizer
      日本癌学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Alteration of tumor microenvironment and radioresistance induced by clonal hematopoiesis2021

    • Author(s)
      立川 章太郎 , 元岡 大祐 , 玉利 慶介 , 皆巳 和賢 , 瀬尾 雄二 , 高橋 豊 , 今野 雅允 , 石井 秀始 , 猪原 秀典 , 小川 和彦
    • Organizer
      日本血液学会学術集会
    • Related Report
      2021 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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