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Study of optimally combined immunotherapy based on analysis of Intratumor Immune response in sarcoma

Research Project

Project/Area Number 20K18080
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionJapanese Foundation for Cancer Research

Principal Investigator

SATO Yasuyoshi  公益財団法人がん研究会, 有明病院 総合腫瘍科, 副医長 (00869836)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2021: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2020: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords肉腫 / 腫瘍免疫 / 免疫療法 / 免疫応答 / イムノグラム / 腫瘍内免疫応答 / バイオマーカー
Outline of Research at the Start

本研究では、肉腫患者の腫瘍組織検体と血液検体を用いて、次世代シークエンサー、フローサイトメトリー、液性因子解析により腫瘍内免疫応答を多層的に解析し、患者個々の腫瘍内免疫応答の特性を評価した「イムノグラム」を作成することで、肉腫における腫瘍内免疫応答の特徴を解明し、免疫療法が奏効する患者群を選別し、さらに患者個々への最適な複合的免疫治療の提供を目指す。

Outline of Final Research Achievements

Surgical and peripheral blood samples were collected from 180 sarcoma patients during the study period. In cases where a sufficient amount of tumor tissue could be obtained, the tumor tissue was shredded and enzymatically treated to produce fresh tumor digest (FTD). The remainder was seeded on a culture medium to culture tumor-infiltrating lymphocytes (TILs) and tumor cells. The resulting TILs and FTD were co-cultured, and the supernatant was collected and analyzed for interferon gamma (IFNγ) production by ELISA, confirming the presence of a case group of tumor-reactive TILs in the tumor cells as in previous studies. In addition, next-generation sequencing has been outsourced, and flow cytometry and liquid factor analysis have been performed in some cases to analyze the multilayered immune response within the tumor.

Academic Significance and Societal Importance of the Research Achievements

肉腫においても腫瘍細胞内に腫瘍反応性のTILが存在する症例があることが確認された。研究期間終了時点では、次世代シークエンス、フローサイトメトリー、液性因子解析を行って、腫瘍内免疫応答の多層的な解析を進めており、最終的には、腫瘍内免疫応答の評価に基づく個別化免疫治療や新規の複合的免疫治療の開発につながることが期待される。

Report

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

    (14 results)

All 2023 2022 2021 2020

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results) Presentation (9 results) (of which Int'l Joint Research: 4 results)

  • [Journal Article] Changes in Neutrophil-to-lymphocyte Ratio Predict Efficacy of Trabectedin for Soft-tissue Sarcoma2021

    • Author(s)
      SATO YASUYOSHI、NAKANO KENJI、KAWAGUCHI KUNIKI、FUKUDA NAOKI、WANG XIAOFEI、URASAKI TETSUYA、OHMOTO AKIHIRO、HAYASHI NAOMI、YUNOKAWA MAYU、ONO MAKIKO、TOMOMATSU JUNICHI、HAYAKAWA KEIKO、FUNAUCHI YUKI、TANIZAWA TAISUKE、AE KEISUKE、MATSUMOTO SEIICHI、TAKAHASHI SHUNJI
    • Journal Title

      Cancer Diagnosis & Prognosis

      Volume: 1 Issue: 4 Pages: 303-308

    • DOI

      10.21873/cdp.10040

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pre-Treatment Neutrophil-to-Lymphocyte Ratio (NLR) as a Predictive Marker of Pazopanib Treatment for Soft-Tissue Sarcoma2021

    • Author(s)
      Sato Yasuyoshi、Nakano Kenji、Wang Xiaofei、Fukuda Naoki、Urasaki Tetsuya、Ohmoto Akihiro、Hayashi Naomi、Yunokawa Mayu、Ono Makiko、Tomomatsu Junichi、Saito Masanori、Minami Yusuke、Hayakawa Keiko、Funauchi Yuki、Tanizawa Taisuke、Ae Keisuke、Matsumoto Seiichi、Takahashi Shunji
    • Journal Title

      Cancers

      Volume: 13 Issue: 24 Pages: 6266-6266

    • DOI

      10.3390/cancers13246266

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pre-treatment Neutrophil-to-Lymphocyte Ratio Predicts Efficacy of Eribulin for Soft-tissue Sarcoma2021

    • Author(s)
      SATO YASUYOSHI、NAKANO KENJI、FUKUDA NAOKI、WANG XIAOFEI、URASAKI TETSUYA、OHMOTO AKIHIRO、YUNOKAWA MAYU、ONO MAKIKO、TOMOMATSU JUNICHI、HAYAKAWA KEIKO、FUNAUCHI YUKI、TANIZAWA TAISUKE、AE KEISUKE、MATSUMOTO SEIICHI、TAKAHASHI SHUNJI
    • Journal Title

      Anticancer Research

      Volume: 41 Issue: 1 Pages: 527-532

    • DOI

      10.21873/anticanres.14804

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Integrative immunogenomic analysis of gastric cancer dictates novel immunological classification and the functional status of tumor‐infiltrating cells2020

    • Author(s)
      Sato Y、Wada I、Odaira K、Hosoi A、Kobayashi Y、Nagaoka K、Karasaki T、Matsushita H、Yagi K、Yamashita H、Fujita M、Watanabe S、Kamatani T、Miya F、Mineno J、Nakagawa H、Tsunoda T、Takahashi S、Seto Y、Kakimi K
    • Journal Title

      Clinical & Translational Immunology

      Volume: 9 Issue: 10 Pages: 9-9

    • DOI

      10.1002/cti2.1194

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] An analysis of tumor infiltrating lymphocyte in sarcoma for immunotherapy2020

    • Author(s)
      船内 雄生、佐藤 靖祥、垣見 和宏、高橋 俊二、阿江 啓介、大川 淳
    • Journal Title

      Journal of the Eastern Japan Association of Orthopaedics and Traumatology

      Volume: 32 Issue: 1 Pages: 79-82

    • DOI

      10.24645/jejot.32.1_79

    • NAID

      130007837492

    • ISSN
      1342-7784, 2433-569X
    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] がん専門病院での肉腫における遺伝子パネル検査の現状2023

    • Author(s)
      佐藤 靖祥
    • Organizer
      第6回日本サルコーマ治療研究学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 統合的免疫ゲノム解析に基づく頭頸部癌の新規免疫学的分類.2022

    • Author(s)
      佐藤靖祥, 瀬戸陽, 小林由香利, 長岡孝治, 仲野兼司, 佐藤由紀子, 神山亮介, 新橋渉, 佐々木徹, 福島啓文, 米川博之, 高橋俊二, 三谷浩樹, 垣見和宏
    • Organizer
      第19回日本臨床腫瘍学会学術集会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Biomarkers by integrative immunogenomic analysis before and after nivolumab in gastric cancer2022

    • Author(s)
      Yasuyoshi Sato, Yukari Kobayashi, Koji Nagaoka, Yasuhiro Okumura, Koichi Yagi, Hiroharu Yamashita, Kazuhiro Kakimi, Yasuyuki Seto
    • Organizer
      第94回日本胃癌学会総会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Analysis of intra-tumoral immune response before and after nivolumab treatment in gastric cancer:胃癌におけるニボルマブ治療前後の腫瘍内免疫応答の解析.2021

    • Author(s)
      佐藤靖祥, 山下裕玄, 小林由香利, 長岡孝治, 高橋俊二, 瀬戸泰之, 垣見和宏
    • Organizer
      第80回日本癌学会学術総会
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 免疫ゲノム解析による胃癌の新規免疫学的分類2021

    • Author(s)
      佐藤靖祥、和田郁雄、小林由香利、奥村康弘、若松高太郎、八木浩一、愛甲丞、山下裕玄、野村幸世、垣見和宏、瀬戸泰之
    • Organizer
      第93回日本胃癌学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Novel immunological classification of gastric cancer by integrative analysis2020

    • Author(s)
      Sato Y、Wada I、Odaira K、Hosoi A、Kobayashi Y、Nagaoka K、Karasaki T、Matsushita H、Yagi K、Yamashita H、Takahashi S、Seto Y、Kakimi K
    • Organizer
      AACR2020 VIRTUAL ANNUALMEEING II
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 統合的な解析による新たな胃がんの免疫学的分類2020

    • Author(s)
      小林由香利、佐藤靖祥、和田郁雄、細井亮宏、長岡孝治、八木浩一、山下裕玄、高橋俊二、瀬戸泰之、垣見和宏
    • Organizer
      第79回日本癌学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] 肉腫における腫瘍内免疫微小環境の解析2020

    • Author(s)
      小林由香利、佐藤靖祥、船内雄生、細井亮宏、唐崎隆弘、高橋俊二、阿江啓介、垣見和宏
    • Organizer
      第24回日本がん免疫学会総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 胃がんの腫瘍内免疫応答の統合的解析2020

    • Author(s)
      細井亮宏、佐藤靖祥、長岡孝治、小林由香利、高橋俊二、瀬戸泰之、垣見和宏
    • Organizer
      第24回日本がん免疫学会総会
    • Related Report
      2020 Research-status Report

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

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