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A novel antitumor immunotherapy to break the tolerance induced in small cell lung cancer patients

Research Project

Project/Area Number 18590841
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionNiigata University

Principal Investigator

KAGAMU Hiroshi  Niigata University, Institute of Medicine and Dentistry, Assistant Professor (30418686)

Co-Investigator(Kenkyū-buntansha) NAKATA Koh  Niigata University, Medical and Dental Hospital, Professor (80207802)
YOSHIZAWA Hirohisa  Niigata University, Medical and Dental Hospital, Associate Professor (50282984)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,690,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordssmall cell lung cancer / regulatory T cell / antitumor effector CD4 T cell / 抗腫瘍エフェクターCD4T細胞
Research Abstract

Small cell lung cancer (SCLC) possesses high tendency to disseminate. However, SCLC patients with paraneoplastic syndrome mediated by immunity against onconeural antigens remain in limited-stage disease (LD) without distant metastases. Cumulative evidence regulates that a balance between immune and regulatory T cells (Treg) determines the magnitude of immune responses to not only self-antigens but also tumor-associated antigens. Here, we analyzed T cells in the peripheral blood of 35 consecutive SCLC patients, 8 long-term survivors, and 19 healthy volunteers to assess the balance of CD4^+ T cells. Purified CD4^+ T cells with down-regulated expression of CD62L (CD62L^(low)) produced IFN-γ, IL-4, and IL-17, thus, considered to be immune effector T cells (Teff). Significantly more Teff numbers were detected in LD-SCLC patients than that of extended-stage SCLC (ED-SCLC). By contrast, induction of CD62L^(high) CD25^+ CD4^+ Treg was significantly higher in ED-SCLC patients than that of LD-SCLC patients. Analyses of cytokine secretion revealed that Teff in LD-SCLC patients produced significantly more IL-17 and that dendritic cells derived from CD14^+ cells of LD-SCLC patients secreted more IL-23. Long-term survivors of SCLC maintained a high Teff to Treg ratio, whereas patients with recurrent disease exhibited a low Teff to Treg ratio. Therefore, we concluded that CD4^+ T cell balance may be a biomarker that distinguishes ED-SCLC from LD-SCLC and predicts recurrence. This study also suggests the importance of inducing effector CD4^+ T cells, particularly Th17 cells, while eliminating Treg to control systemic dissemination of SCLC.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (13 results)

All 2008 2007

All Journal Article (7 results) (of which Peer Reviewed: 4 results) Presentation (6 results)

  • [Journal Article] Appropriate timing of CD40 ligation for RNA-pulsed DCs to induce antitumor immunity2008

    • Author(s)
      Satoshi Miura, Hiroshi Kagamu, Hiroshi Tanaka, Hirohisa Yoshizawa, Fumitake Gejyo
    • Journal Title

      Scandinavian Journal of Immunology 67

      Pages: 385-391

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Appropriate timing of CD40 ligation for RNA-pulsed DCs to induce antitumor immunity2008

    • Author(s)
      Satoshi, Miura, Hiroshi, Kagamu, Hiroshi, Tanaka, Hirohisa, Yoshizawa, Fumitake, Gejyo
    • Journal Title

      Scandinavian Journal of Immunology 67

      Pages: 385-391

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Generation of anti-tumor effctor T cells from naive T cells by stimulation with dendritic/tumor fusion cells.2007

    • Author(s)
      Akira Ishida, Hiroshi Tanaka, Toru Hiura, Satoshi Miura, Satoshi Watanabe, Koki Matsuyama, Hideyuki Kuriyama, Junta Tanaka, Hiroshi Kagamu, Fumitake Gejyo, Hirohisa Yoshizawa
    • Journal Title

      Scandinavian Journal of Immunology 66

      Pages: 546-554

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Anti-cytokine autoantibodies are ubiquitous in healthy individuals2007

    • Author(s)
      Masato Watanabe, Kanji Uchida, Kazuhide Nakagaki, Hiroko Kanazawa, Bruce C. Trapnell, Yoshihiko Hoshino, Hiroshi Kagamu, Hirohisa Yoshizawa, Naoto Keicho, Hajime Goto, Koh Nakata
    • Journal Title

      FEBS letters 581

      Pages: 2017-2021

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Generation of anti-tumor effector T cells from naive T cells by stimulation with dendritic/tumor fusion cells2007

    • Author(s)
      Akira, Ishida, Hiroshi, Tanaka, Toru, Hiura, Satoshi, Miura, Satoshi, Watanabe, Koki, Matsuyama, Hideyuki, Kuriyama, Junta, Tanaka, Hiroshi, Kagamu, Fumitake, Geiyo, Hirohisa, Yoshizawa
    • Journal Title

      Scandinavian Journal of Immunology 66

      Pages: 546-554

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Anti-cytokine autoantibodies are ubiquitous in healthy individuals2007

    • Author(s)
      Masato, Watanabe., Kanji, Uchida., Kazuhide. Nakagaki., Hiroko. Kanazawa., Bruce C, Trapnell., Yoshihiko. Hoshino, Hiroshi. Kagamu, Hirohisa. Yoshizawa, Naoto. Keicho, Hajime. Goto, Koh. Nakata
    • Journal Title

      FEBS letters 581

      Pages: 2017-2021

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Generation of anti-tumor effector T cells from naive T cells by stimulation with dendritic/tumor fusion cells.2007

    • Author(s)
      Akira Ishida, Hiroshi Tanaka, Toru Hiura, Satoshi Miura, Satoshi Watanabe, Koki Matsuyama, Hideyuki Kuriyama, Junta Tanaka, Hiroshi Kagamu, Fumitake Gejyo, Hirohisa Yoshizawa
    • Journal Title

      Scandinavian Journal of Immunology 66

      Pages: 546-554

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Presentation] CD4+effector T cells specific for irrelevant peptides can induce antitumor reactivity via epitope spreading2007

    • Author(s)
      小山建一、各務博
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-03
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] CD4+ effector T cells specific for irrelevant peptides can induce antitumor reactivity via epitope spreading2007

    • Author(s)
      Kenichi, Koyama, Hirohi, Kagamu, et. al.
    • Organizer
      Japanese Cancer Association, annual meeting
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      2007-10-03
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] CD4+ effector T cells specific for irrelevant peptides can induce antitumor reactivity via epitope spreading2007

    • Author(s)
      小山建一、各務博
    • Organizer
      日本癌学会
    • Place of Presentation
      横浜
    • Year and Date
      2007-10-03
    • Related Report
      2007 Annual Research Report
  • [Presentation] OVA peptide-responsive CD4+effector T cells can induce antitumor immunity via epitope spreading mediated by dendritic cells2007

    • Author(s)
      小山建一、各務博
    • Organizer
      American Association for Cancer Research
    • Place of Presentation
      Los Angeles, USA
    • Year and Date
      2007-04-16
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] OVA peptide-responsive CD4^+ effector T cells can induce antitumor immunity via epitope spreading mediated by dendritic cells2007

    • Author(s)
      Kenichi, Koyama, Hiroshi, Kagamu, et. al.
    • Organizer
      American Association for Cancer Research, annual meeting
    • Place of Presentation
      Los Angeles, USA
    • Year and Date
      2007-04-16
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] OVA peptide-responsive CD4^+ effector T cells can induce antitumor immunity via epitope spreading mediated by dendritic cells2007

    • Author(s)
      小山建一、各務博
    • Organizer
      American Association for Cancer Research
    • Place of Presentation
      Los Angeles, USA
    • Year and Date
      2007-04-16
    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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