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Elucidation of molecular mechanism of T cell terminal differentiation lineage for cancer immunotherapy

Research Project

Project/Area Number 17K07215
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

Fujiki Fumihiro  大阪大学, 医学系研究科, 特任准教授(常勤) (40456926)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywordsターミナルエフェクター / 癌免疫療法 / がん免疫療法 / メモリーT細胞 / ターミナルエフェクターT細胞 / 免疫学 / 癌
Outline of Final Research Achievements

Efficient induction of memory T cells are required for optimal anti-tumor immune response. In this study, we identified a novel gene responsible for terminal effector T cell differentiation. Overexpression of the gene in T cells attenuated the expression of CD62L, proliferation capacity, and the resistance to apoptosis. Furthermore, the knockdown of the gene restored them in terminal effector T cells. Thus, the gene should be a promising target for enhancing cancer immunotherapy.

Academic Significance and Societal Importance of the Research Achievements

近年、癌免疫療法は癌治療の一つとして急速に発展してきた。しかしながら、その効果は限定的であり、その理由の一つとして患者の癌細胞を攻撃する免疫細胞の「質」が低下していることが明らかとなっている。本研究では、この免疫細胞の「質」が低下する責任遺伝子を同定した。この成果は将来、より強力な癌免疫療法の開発につながると期待される。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (20 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (1 results) Journal Article (10 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 10 results,  Open Access: 9 results) Presentation (9 results) (of which Int'l Joint Research: 3 results)

  • [Int'l Joint Research] Antwerp University(ベルギー)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Reader-free ELISPOT assay for immuno-monitoring in peptide-based cancer vaccine immunotherapy2020

    • Author(s)
      Hayashi Sae、Imanishi Rin、Adachi Mayuko、Ikejima Sayaka、Nakata Jun、Morimoto Soyoko、Fujiki Fumihiro、Nishida Sumiyuki、Tsuboi Akihiro、Hosen Naoki、Nakajima Hiroko、Hasegawa Kana、Oka Yoshihiro、Sugiyama Haruo、Oji Yusuke
    • Journal Title

      Biomedical Reports

      Volume: 12 Pages: 244-250

    • DOI

      10.3892/br.2020.1289

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immune adjuvant therapy using Bacillus Calmette-Guérin cell wall skeleton (BCG-CWS) in advanced malignancies: A phase 1 study of safety and immunogenicity assessments.2019

    • Author(s)
      Nishida S, Tsuboi A, Tanemura A, Ito T, Nakajima H, Shirakata T, Morimoto S, Fujiki F, Hosen N, Oji Y, Kumanogoh A, Kawase I, Oka Y, Azuma I, Morita S, Sugiyama H.
    • Journal Title

      Medicine (Baltimore)

      Volume: 98 Issue: 33 Pages: e16771-e16771

    • DOI

      10.1097/md.0000000000016771

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A phase I clinical study of a cocktail vaccine of Wilms’ tumor 1 (WT1) HLA class I and II peptides for recurrent malignant glioma2018

    • Author(s)
      Tsuboi A, Hashimoto N, Fujiki F, Morimoto S, Kagawa N, Nakajima H, Hosen N, Nishida S, Nakata J, Morita S, Sakamoto J, Oji Y, Oka Y, Sugiyama H
    • Journal Title

      Cancer Immunology, Immunotherapy

      Volume: 68(2) Issue: 2 Pages: 331-340

    • DOI

      10.1007/s00262-018-2274-1

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extremely strong infiltration of WT1-specific CTLs into mouse tumor by the combination vaccine with WT1-specific CTL and helper peptides2018

    • Author(s)
      Nakata Jun、Nakajima Hiroko、Hayashibara Hiromu、Imafuku Kanako、Morimoto Soyoko、Fujiki Fumihiro、Motooka Daisuke、Okuzaki Daisuke、Hasegawa Kana、Hosen Naoki、Tsuboi Akihiro、Oka Yoshihiro、Kumanogoh Atsushi、Oji Yusuke、Sugiyama Haruo
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 89 Pages: 36029-36038

    • DOI

      10.18632/oncotarget.26338

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Efficient and Non-genotoxic RNA-Based Engineering of Human T Cells Using Tumor-Specific T Cell Receptors With Minimal TCR Mispairing2018

    • Author(s)
      Campillo-Davo Diana、Fujiki Fumihiro、Van den Bergh Johan M. J.、De Reu Hans、Smits Evelien L. J. M.、Goossens Herman、Sugiyama Haruo、Lion Eva、Berneman Zwi N.、Van Tendeloo Viggo
    • Journal Title

      Frontiers in Immunology

      Volume: 9

    • DOI

      10.3389/fimmu.2018.02503

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Establishment of a novel platform cell line for efficient and precise evaluation of T cell receptor functional avidity2018

    • Author(s)
      Morimoto Soyoko、Fujiki Fumihiro、Kondo Kenta、Nakajima Hiroko、Kobayashi Yoshiki、Inatome Miki、Aoyama Nao、Nishida Yuya、Tsuboi Akihiro、Oka Yoshihiro、Nishida Sumiyuki、Nakata Jun、Hosen Naoki、Oji Yusuke、Sugiyama Haruo
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 75 Pages: 34132-34141

    • DOI

      10.18632/oncotarget.26139

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A versatile T cell-based assay to assess therapeutic antigen-specific PD-1-targeted approaches2018

    • Author(s)
      Versteven Maarten、Bergh Johan M.J. Van den、Broos Katrijn、Fujiki Fumihiro、Campillo-Davo Diana、De Reu Hans、Morimoto Soyoko、Lecocq Quentin、Keyaerts Marleen、Berneman Zwi、Sugiyama Haruo、Van Tendeloo Viggo F.I.、Breckpot Karine、Lion Eva
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 45 Pages: 27797-27808

    • DOI

      10.18632/oncotarget.25591

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] WT1 peptide-based immunotherapy for advanced thymic epithelial malignancies2018

    • Author(s)
      Oji Y、Inoue M、Takeda Y、Hosen N、Shintani Y、Kawakami M、Harada T、Murakami Y、Iwai M、Fukuda M、Nishida S、Nakata J、Nakae Y、Takashima S、Shirakata T、Nakajima H、Hasegawa K、Kida H、Kijima T、Morimoto S、Fujiki F、Tsuboi A、Morii E、Morita S、Sakamoto J、Kumanogoh A、Oka Y、Okumura M、Sugiyama H
    • Journal Title

      International Journal of Cancer

      Volume: 142 Issue: 11 Pages: 2375-2382

    • DOI

      10.1002/ijc.31253

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combination Gemcitabine and WT1 Peptide Vaccination Improves Progression-Free Survival in Advanced Pancreatic Ductal Adenocarcinoma: A Phase II Randomized Study.2018

    • Author(s)
      Nishida S, Ishikawa T, Egawa S, Koido S, Yanagimoto H, Ishii J, Kanno Y, Kokura S, Yasuda H, Oba MS, Sato M, Morimoto S, Fujiki F, Eguchi H, Nagano H, Kumanogoh A, Unno M, Kon M, Shimada H, Ito K, Homma S, Oka Y, Morita S, Sugiyama H.
    • Journal Title

      Cancer Immunol Res.

      Volume: 6 Issue: 3 Pages: 320-331

    • DOI

      10.1158/2326-6066.cir-17-0386

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia2017

    • Author(s)
      Anguille Sebastien、et al
    • Journal Title

      Blood

      Volume: 130 Issue: 15 Pages: 1713-1721

    • DOI

      10.1182/blood-2017-04-780155

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Comparison of WT1-specific T cell responses in recurrent glioma patients received CTL + Helper peptide vaccine vs CTL peptide vaccine alone2019

    • Author(s)
      Fumihiro Fujiki, Akihiro Tsuboi, Soyoko Morimoto, Naoya Hashimoto, Miki Inatome, Yoshihiro Oka, Yusuke Oji, Haruo Sugiyama
    • Organizer
      International Conference on WT1 Biology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Establishment of a novel platform cell line for efficient and precise evaluation of T cell receptor functional avidity and its application2019

    • Author(s)
      Soyoko Morimoto, Fumihiro Fujiki, Maarten Versteven, Kenta Kondo, Hiroko Nakajima, Yoshiki Kobayashi, Miki Inatome, Nao Aoyama, Yuya Nishida, Akihiro Tsuboi, Yoshihiro Oka, Yusuke Oji, Eva Lion, Haruo Sugiyama
    • Organizer
      International Conference on WT1 Biology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 再発脳腫瘍患者におけるWT1ヘルパーペプチド併用WT1ペプチドワクチン療法の免疫モニタリング解析2019

    • Author(s)
      藤木文博、坪井昭博、森本創世子、橋本直哉、稲留美希、中島博子、中田潤、保仙直毅、尾路祐介、岡芳弘、杉山治夫
    • Organizer
      第11回日本血液疾患免疫療法学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 癌抗原特異的T細胞受容体のfunctional avidity を効率よく正確に評価できるplatform細胞の作製とその応用例2019

    • Author(s)
      森本創世子、藤木文博、近藤健太、中島博子、中田潤、保仙直毅、橋井佳子、坪井昭博、岡芳弘、尾路祐介、杉山治夫
    • Organizer
      第11回日本血液疾患免疫療法学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 急性骨髄性白血病に対するWT1ワクチン療法の現状および今後の展望2019

    • Author(s)
      中田潤、中江吉希、川上学、森本創世子、中島博子、藤木文博、西田純幸、保仙直毅、坪井昭博、尾路祐介、岡芳弘、杉山治夫
    • Organizer
      第11回日本血液疾患免疫療法学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 脳腫瘍患者におけるWT1ヘルパーペプチド併用WT1ペプチドワクチン療法の免疫モニタリング解析2019

    • Author(s)
      森本創世子、坪井昭博、藤木文博、橋本直哉、稲留美希、中島博子、中田潤、保仙直毅、尾路祐介、岡芳弘、杉山治夫
    • Organizer
      第47回日本臨床免疫学会総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 癌抗原特異的 T 細胞受容体の functional avidity を効率よく正確に評価できる platform 細胞の作製2018

    • Author(s)
      森本創世子
    • Organizer
      第46回日本臨床免疫学会総会
    • Related Report
      2018 Research-status Report
  • [Presentation] Establishment of a novel platform cell line for efficient and precise evaluation of T cell receptor functional avidity2018

    • Author(s)
      Soyoko Morimoto
    • Organizer
      9th International Conference on WT1 in Human Neoplasia
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 切除不能進行膵癌に対するゲムシタビン併用HLA拘束性WT1ペプチドワクチン療法で誘導されたWT1特異的CTLの免疫学的機能解析2017

    • Author(s)
      森本創世子、西田純幸、他
    • Organizer
      第21回日本がん免疫学会総会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2021-02-19  

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