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The estimation of the efficacy of immuno-checkpoint inhibitor in gene mutation for recurrent oral cancer

Research Project

Project/Area Number 19K10337
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 57060:Surgical dentistry-related
Research InstitutionSapporo Medical University

Principal Investigator

Ogi Kazuhiro  札幌医科大学, 医学部, 講師 (40433114)

Co-Investigator(Kenkyū-buntansha) 西山 廣陽  札幌医科大学, 医学部, 助教 (60749563)
宮本 昇  琉球大学, 医学部附属病院, 助教 (80749565)
Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsImmunotherapy / squamous cell carcinoma / gene mutation / 再発口腔がん / 免疫チェックポイント阻害剤 / 遺伝子変異 / がん免疫環境 / 再発口腔癌 / 免疫チェックポイント阻害薬 / 遺伝子変異量
Outline of Research at the Start

我々が開発した口腔癌遺伝子解析パネルをもちいて、口腔扁平上皮癌(凍結組織、FFPE)における遺伝子異常を効率的、かつ低コストで行い、治療抵抗性、再発・予後との相関を分析する。遺伝子異常(遺伝子変異、コピー数異常)は実験的に評価し、口腔癌の発症、進展への関与を解析する。これらの成果をもとに、従来の評価法を補完しうる、血清、末梢循環DNAを用いた、口腔癌の新しい診断・治療予測システムを開発する。本研究の主眼は免疫チェックポイント阻害薬の適応症例を選択するにあたり、遺伝子変異量や新たなneoantigenの存在が潜在マーカーを症例ごとにプロファイリングする。

Outline of Final Research Achievements

The indications of immune checkpoint inhibitors (ICIs) are mainly for recurrent oral cancer. It carefully requires the assessment of the slowly continuous therapeutic effects after administration of ICIs, and the switching from ICIs to cytotoxic anticancer agents or to molecular-targeted agents. In addition, there are no evidence regarding to the administration period. Also, it shows a delayed effect, and prolong a long time until it occurs a tumor immune response. In our research, we were able to verify the relevance of tumor-infiltrating lymphocytes (TIL) and somatic gene mutations in our clinical specimens, resulting from the exploration of some factors for predicting the therapeutic effect of ICI.

Academic Significance and Societal Importance of the Research Achievements

再発口腔癌に対して, ICI投与前にがん関連遺伝子変異を調べてICIの有効性を検証することができる. これによりirAEなどの有害事象の軽減に繋がり, がん免疫療法を適正な治療法として確立することができる.

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (14 results)

All 2022 2021 2020 2019

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 5 results) Presentation (8 results) Book (1 results)

  • [Journal Article] Prognostic value of CD45Ro+ T-cell expression in patients with oral squamous cell carcinoma2021

    • Author(s)
      Koike Kazushige, Nishiyama Koyo, Dehari Hironari, Ogi Kazuhiro, Sasaki Takanori, Shimizu Shota, Sasaya Takashi, Tsuchihashi Kei, Sonoda Tomoko, Hasegawa Tadashi, Hiratsuka Hiroyoshi, Miyazaki Akihiro.
    • Journal Title

      Anticancer Res.

      Volume: 41(9) Issue: 9 Pages: 4515-4522

    • DOI

      10.21873/anticanres.15262

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] DLEU1 promotes oral squamous cell carcinoma progression by activating interferon-stimulated genes2021

    • Author(s)
      Hatanaka Yui、Niinuma Takeshi、Kitajima Hiroshi、Nishiyama Koyo、Maruyama Reo、Ishiguro Kazuya、Toyota Mutsumi、Yamamoto Eiichiro、Kai Masahiro、Yorozu Akira、Sekiguchi Shohei、Ogi Kazuhiro、Dehari Hironari、Idogawa Masashi、Sasaki Yasushi、Tokino Takashi、Miyazaki Akihiro、Suzuki Hiromu
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 20438-20438

    • DOI

      10.1038/s41598-021-99736-5

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic value of HLA class Ⅰ expression in patients with oral squamous cell carcinoma2020

    • Author(s)
      Koike K, Dehari H, Shimizu S, Nishiyama K, Sonoda T, Ogi K, Kobayashi J, Sasaki T, Sasaya T, Tsuchihashi K, Tsukahara T, Hasegawa T, Torigoe T, Hiratsuka H, Miyazaki A
    • Journal Title

      Cancer Sci

      Volume: in press Issue: 5 Pages: 1491-1499

    • DOI

      10.1111/cas.14388

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prognostic value of FoxP3 and CTLA-4 expression in patients with oral squamous cell carcinoma2020

    • Author(s)
      Koike Kazushige、Dehari Hironari、Ogi Kazuhiro、Shimizu Shota、Nishiyama Koyo、Sonoda Tomoko、Sasaki Takanori、Sasaya Takashi、Tsuchihashi Kei、Hasegawa Tadashi、Torigoe Toshihiko、Hiratsuka Hiroyoshi、Miyazaki Akihiro
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 8 Pages: e0237465-e0237465

    • DOI

      10.1371/journal.pone.0237465

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Chemotherapy after progression on nivolumab is essential for responders with genetic alterations of driver gene: Review of two recurrent/metastatic squamous cell carcinoma patients2020

    • Author(s)
      荻 和弘
    • Journal Title

      Oral Oncology

      Volume: 102

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 再発口腔癌におけるPD-L1, CD8の発現の意義とNOTCHシグナルを介したがん免疫機構の解析2022

    • Author(s)
      荻 和弘,岩本空大,笹谷 聖,小池和茂,岡本準也,金子 剛,佐々木敬則,出張裕也,中井裕美,宮﨑晃亘
    • Organizer
      第46回日本頭頸部癌学会総会・学術講演会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Predictive assesment of ctDNA monitoring of tongue carcinoma patient with nivolumab responder2022

    • Author(s)
      荻 和弘、岩本空大、西山廣陽、高田弘一、染谷正則、宮﨑晃亘
    • Organizer
      第60回日本癌治療学会学術集会
    • Related Report
      2022 Annual Research Report
  • [Presentation] 全エクソーム解析によるがん遺伝子変異と臨床効果との関連性が示唆された舌癌の1例2021

    • Author(s)
      荻 和弘、岩本空大、笹谷 聖、西山廣陽、岡本準也、金子 剛、佐々木敬則、出張裕也、中井裕美、宮﨑晃亘
    • Organizer
      第40回日本口腔腫瘍学会総会・学術大会
    • Related Report
      2021 Research-status Report
  • [Presentation] 口腔扁平上皮癌における腫瘍浸潤リンパ球の局在と予後との関連性についての研究2020

    • Author(s)
      小池和茂、出張裕也、荻 和弘、西山廣陽、佐々木敬則、土橋 恵、笹谷 聖、中井裕美、岡本準也、宮﨑晃亘
    • Organizer
      第65回日本口腔外科学会総会・学術大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Prognostic impact of HLA class I expression and its association with CD8 T-cell density in patients with oral squamous cell carcinoma2020

    • Author(s)
      Koike K, Dehari H, Ogi K, Shimizu S, Nishiyama K, Sonoda T, Sasaki T, Sasaya T, Tsuchihashi K, Hasegawa T, Torigoe T, Hiratsuka H, Miyazaki A
    • Organizer
      第79回日本癌学会学術総会
    • Related Report
      2020 Research-status Report
  • [Presentation] 再発または遠隔転移を有する口腔癌に対しニボルマブ投与は遺伝子変異が指標となるか2020

    • Author(s)
      荻 和弘、小林淳一、西山廣陽、小池和茂、高田弘一、染谷正則、宮﨑晃亘
    • Organizer
      第58回日本癌治療学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] IgG関連疾患が疑われる頸部リンパ節腫大の1症例2019

    • Author(s)
      千種 達也、荻 和弘ら
    • Organizer
      第45回日本口腔外科学会北日本支部学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 口腔扁平上皮癌における制御性T細胞の発現に関する免疫組織化学的検討2019

    • Author(s)
      小池和茂、荻 和弘ら
    • Organizer
      第78回日本癌学会学術総会
    • Related Report
      2019 Research-status Report
  • [Book] Precision Medicine 2020年12月号 口腔癌に対する免疫療法: 個別化・複合免疫療法の臨床応用に向けての研究2020

    • Author(s)
      宮﨑 晃亘, 荻 和弘, 小池 和茂, 岡本 準也, 出張 裕也, 中井 裕美
    • Total Pages
      94
    • Publisher
      北隆館
    • Related Report
      2020 Research-status Report

URL: 

Published: 2019-04-18   Modified: 2024-01-30  

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