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Development of prediction of responder in cancer immunotherapy by using radiation

Research Project

Project/Area Number 16K07173
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Tumor therapeutics
Research InstitutionOsaka University

Principal Investigator

Takahashi Yutaka  大阪大学, 医学系研究科, 特任講師(常勤) (40353461)

Co-Investigator(Kenkyū-buntansha) 玉利 慶介  大阪大学, 医学系研究科, 特任助教(常勤) (30718995)
小川 和彦  大阪大学, 医学系研究科, 教授 (40253984)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords放射線 / 重粒子線 / 腫瘍免疫 / アブスコパル効果 / X線 / 抗腫瘍免疫 / 免疫チェックポイント阻害剤
Outline of Final Research Achievements

Immune checkpoint inhibitor has been playing an important role in controlling metastatic tumors. However, only limited patients experience durable response. Therefore development of strategy to increase the responder and exploring biomarker to predict the responder is an urgent issue. The purpose of this study was to investigate whether use of various radiation including X-ray and particle beam combined with dual immune checkpoint blockade (Anti-PD-L1 and anti-CTLA-4 antibodies: P1C4) contribute to the control of tumors out-side radiation field, and addition of radiation to immune checkpoint blockade alters immune micro environment. We found that both X-ray and carbon ion irradiation enhanced the efficacy of P1C4 both for irradiated tumors and tumors out-of-radiation field with the increase of CD8 to Treg ratio. Although further study is necessary, tumor microenvironment analysis after radiation therapy might be useful to predict responder for immune checkpoint blockade therapy.

Academic Significance and Societal Importance of the Research Achievements

免疫チェックポイント阻害剤は遠隔転移を有する症例に対しても効果が得られているが、奏効率は依然と低く、高奏効率化と予測法の開発が求められている。私たちは、まず、X線、または重粒子線と免疫チェックポイント阻害剤を併用することで、奏効率の向上が得られるかどうかを骨肉腫マウスモデルを用い、骨肉腫細胞を両脚に移植し、片方のみに照射する系で研究した。その結果、放射線と抗PD-L1抗体と抗CTLA-4抗体を併用することで、照射腫瘍のみならず、照射野外の腫瘍に対しても高率に抗腫瘍効果が得られ、有意に生存が延長し、腫瘍免疫環境も変化していた。本研究は放射線と免疫療法の併用の臨床利用の合理性を与えるものである。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (11 results)

All 2019 2018 2017 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 2 results) Presentation (7 results) (of which Int'l Joint Research: 3 results,  Invited: 2 results) Remarks (1 results)

  • [Journal Article] Carbon ion irradiation enhances the antitumor efficacy of dual immune checkpoint blockade therapy both for local and distant sites in murine osteosarcoma2019

    • Author(s)
      Yutaka Takahashi, Tomohiro Yasui, Kazumasa Minami, Keisuke Tamari, Kazuhiko Hayashi, Keisuke Otani, Yuji Seo, Fumiaki Isohashi, Masahiko Koizumi and Kazuhiko Ogawa
    • Journal Title

      Oncotarget

      Volume: 10(6) Pages: 633-646

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Radiation enhanced the local and distant anti-tumor efficacy in dual immune checkpoint blockade therapy in osteosarcoma2017

    • Author(s)
      Takahashi Yutaka、Yasui Tomohiro、Tamari Keisuke、Minami Kazumasa、Otani Keisuke、Isohashi Fumiaki、Seo Yuji、Kambe Ryosuke、Koizumi Masahiko、Ogawa Kazuhiko
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 12 Pages: e0189697-e0189697

    • DOI

      10.1371/journal.pone.0189697

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Radiation Enhances the Efficacy of Antitumor Immunotherapy with an Immunocomplex of Interleukin-2 and its Monoclonal Antibody2017

    • Author(s)
      Takahashi Y, Yasui T, Minami K, Tamari K, Otani K, Seo Y, Isohashi F, Koizumi M, Ogawa K.
    • Journal Title

      Anticancer Research

      Volume: 37 Issue: 12 Pages: 6799-6806

    • DOI

      10.21873/anticanres.12140

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 骨肉腫に対する放射線治療と免疫チェックポイント阻害剤の最適な併用法2019

    • Author(s)
      武中渉、高橋豊、皆巳和賢、玉利慶介、林和彦、大谷啓祐、瀬尾雄二、礒橋文明、小泉雅彦、小川和彦
    • Organizer
      第21回 菅原・大西記念 がん治療増感シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] Transnational Research and Radiation Biology2018

    • Author(s)
      Yutaka Takahashi
    • Organizer
      Hokkaido Summer Institute 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 炭素イオン照射と二種のチェックポイント阻害剤の併用による、局所および遠隔腫瘍に対する抗腫瘍効果の検討2018

    • Author(s)
      安井智洋、高橋豊、皆巳和賢、玉利慶介、林和彦、大谷啓祐、瀬尾雄二、礒橋文明、小泉雅彦、小川和彦
    • Organizer
      第20回 菅原・大西記念 がん治療増感シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Presentation] Combination of carbon ion irradiation with dual immune checkpoint blockade therapy enhances local and distant antitumor efficacy2018

    • Author(s)
      Tomohiro Yasui, Yutaka Takahashi, Keisuke Tamari, Kazumasa Minami, Keisuke Otani, Fumiaki Isohashi, Kazuhiko Ogawa, Masahiko Koizumi
    • Organizer
      The 1st International Cancer Research Symposium of Training Plan for Oncology Professionals
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 骨肉腫に対する放射線と2種類の免疫チェックポイント阻害剤の併用効果2017

    • Author(s)
      高橋 豊
    • Organizer
      日本放射線腫瘍学会第30回学術大会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Radiation combined with checkpoint blockades enhanced antitumor efficacy for osteosarcoma2017

    • Author(s)
      Yutaka Takahashi, Tomohiro Yasui, Keisuke Tamari, Kazumasa Minami, Keisuke Otani, Fumiaki Isohashi, Yuji Seo, Ryosuke Kambe, Masahiko Koizumi, Kazuhiko Ogawa
    • Organizer
      AACR annual meeting 2017
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Radiation effect on antitumor immunotherapy with an immuno-complex of IL2 and its monoclonal antibody2017

    • Author(s)
      Yutaka Takahashi, Tomohiro Yasui, Keisuke Tamari, Kazumasa Minami, Keisuke Otani, Fumiaki Isohashi, Yuji Seo, Masahiko Koizumi, Kazuhiko Ogawa
    • Organizer
      第46回放射線による制癌シンポジウム
    • Related Report
      2017 Research-status Report
  • [Remarks]

    • URL

      http://www.med.osaka-u.ac.jp/introduction/research/radiology/oncology

    • Related Report
      2017 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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