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Comprehensive analysis of cancer cell response to proton beam using transcriptome analysis

Research Project

Project/Area Number 18K15612
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 52040:Radiological sciences-related
Research InstitutionNational Cancer Center Japan

Principal Investigator

Hojo Hidehiro  国立研究開発法人国立がん研究センター, 東病院, 医員 (60638774)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords粒子線治療 / 免疫応答 / トランスクリプトーム / 食道癌 / 陽子線 / 重粒子線 / 炭素線 / 食道癌細胞 / トランスクリプトーム解析 / 陽子線治療
Outline of Final Research Achievements

We aimed to compare the immune responses after irradiation (IR) with X-ray, protons, and carbon ions in an oesophageal cancer cell line and the underlying mechanisms. An oesophageal cancer cell line, KYSE450, was irradiated with 1 fraction/15 GyE (Gy equivalent) of X-ray, proton, or carbon-ion beams, and then, the cells were harvested for RNA sequencing and gene enrichment analysis. We also knocked out STING and STAT1 in the quest for mechanistic insights. RNA sequencing data revealed that gene expression signatures and biological processes were different in KYSE450 irradiated with X-ray, proton, and carbon-ion beams 24 h after IR. However, after 3 days, a common gene expression signature was detected, associated with biological pathways involved in innate immune responses. Gene knock-out experiments revealed that the STING-STAT1 axis underlies the immune reactions after IR. X-Ray, proton, and carbon-ion IRs induced similar immune responses, regulated by the STING-STAT1 axis.

Academic Significance and Societal Importance of the Research Achievements

がん治療において、陽子線治療や炭素線治療は治療の選択肢の一つとして一般化されつつある。また、免疫チェックポイント阻害剤は放射線治療の増感剤として使用されているが、陽子線、炭素線照射後の免疫応答やそのメカニズムについては不明な点が多い。そこで我々は、それぞれの線質での免疫応答を比較解析する目的で研究を行った。結果、照射後6位時間時点で変動する遺伝子や生物学的経路は3つの線種で異なっていたが、24時間後からその共通性が高くなり、免疫応答関連遺伝子の発現も類似していた。このことから、X線で併用される免疫療法と同様に、陽子線、重粒子線治療との併用でも効果をあげることが期待できると考える。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (2 results)

All 2021 2018

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

  • [Journal Article] Comparative analysis of the immune responses in cancer cells irradiated with X-ray, proton and carbon-ion beams2021

    • Author(s)
      Du Junyan、Kageyama Shun-Ichiro、Hirata Hidenari、Motegi Atsushi、Nakamura Masaki、Hirano Yasuhiro、Okumura Masayuki、Yamashita Riu、Tsuchihara Katsuya、Hojo Hidehiro、Hirayama Ryoichi、Akimoto Tetsuo
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 585 Pages: 55-60

    • DOI

      10.1016/j.bbrc.2021.11.004

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] トランスクリプトーム解析を用いた陽子線に対するがん細胞応答の網羅的解析2018

    • Author(s)
      北條秀博、影山俊一郎、杜君顔、茂木厚、中村匡希、中村直樹、全田貞幹、木部優一、奥村真之、秋元哲夫
    • Organizer
      第47回放射線による制癌シンポジウム
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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