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Establishment of separation method for immunosuppressive neutrophils and antitumor neutrophils in renal cancer and bladder cancer

Research Project

Project/Area Number 17K11122
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Urology
Research InstitutionYamagata University

Principal Investigator

Takeda Yuji  山形大学, 医学部, 准教授 (90302299)

Co-Investigator(Kenkyū-buntansha) 奈良 英利  石巻専修大学, 理工学部, 准教授 (00375338)
黒田 悠太  山形大学, 医学部, 助教 (00594326)
加藤 智幸  山形大学, 医学部, 准教授 (40396560)
土谷 順彦  山形大学, 医学部, 教授 (70282176)
浅尾 裕信  山形大学, 医学部, 教授 (80250744)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords膀胱がん / 炎症 / BCG / 好中球 / 抗腫瘍活性 / MDSCs / MDSCs / 腫瘍学 / 膀胱癌
Outline of Final Research Achievements

In renal cancer patients, immunosuppressive neutrophils called myeloid-derived suppressor cells (MDSCs) appear due to cancerous chronic inflammation. On the other hand, intravesical BCG instillation therapy for non-muscle invasive bladder cancer induces strong inflammation and provides a strong anti-tumor immune response. In this study, we investigated the BCG-induced inflammatory response and tried to find the indicators of neutrophil-like cells associated with anti-tumor immune response. As a result, no increase in MDSCs was observed during the BCG treatment. While, the expression of HLA-II and CXCL10 were increased in neutrophil-like cells in urine. Since it is known that HLA-II and CXCL10 induce activation of the adaptive immune system, it was considered that they could be useful indicators of anti-tumor neutrophil-like cells.

Academic Significance and Societal Importance of the Research Achievements

本研究により、免疫抑制型好中球と抗腫瘍型好中球の指標を得ることが出来た。これは、がん治療の予後予測や適切な治療時期の判断に使用できる可能性がある。具体的には、免疫抑制型好中球が少ない時期を狙って、免疫チェックポイント阻害剤治療を開始する治療方法や、過剰な炎症により免疫抑制型好中球が増加してきた時期には、治療を中断し、がん免疫応答の回復を待つなど、様々ながん治療の最適化を実現できるかもしれない。また、BCGを用いて、体外および体内で『抗腫瘍型好中球』を補完・誘導する免疫治療法に発展できる可能性もある。これらが実現すれば、免疫治療を受ける患者の負担軽減や、医療費削減効果をもたらすと予想できる。

Report

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

    (11 results)

All 2019 2018 2017 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (5 results) (of which Int'l Joint Research: 1 results) Book (1 results) Remarks (2 results)

  • [Journal Article] GPI-80 as a Useful Index for Myeloid Cell Heterogeneity and a Potential Prognostic Biomarker for Metastatic Renal Cell Carcinoma2019

    • Author(s)
      Tomoyuki Kato, Yuji Takeda, Hiromi Ito, Yuta Kurota, Atsushi Yamagishi, Toshihiko Sakurai, Sei Naito, Akemi Araki, Hidetoshi Nara, Hironobu Asao, Norihiko Tsuchiya
    • Journal Title

      The Tohoku Journal of Experimental Medicine

      Volume: 249 Issue: 3 Pages: 203-212

    • DOI

      10.1620/tjem.249.203

    • NAID

      130007751389

    • ISSN
      0040-8727, 1349-3329
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Augmentation of the expression of the eotaxin receptor on duodenal neutrophils by IL-212018

    • Author(s)
      Takeda Yuji、Kato Tomoyuki、Nemoto Nobuhito、Araki Akemi、Gazi Mohammad Yeashin、Nara Hidetoshi、Asao Hironobu
    • Journal Title

      Cytokine

      Volume: 110 Pages: 194-203

    • DOI

      10.1016/j.cyto.2018.05.007

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Analysis of signal transducers using flow cytometry is useful for detection of contractive and fluctuating signals2017

    • Author(s)
      Takeda Y, Nara H, Asao H.
    • Journal Title

      Bulletin of the Yamagata University. Medical science : Yamagata medical journal

      Volume: 35 Pages: 21-32

    • NAID

      120006334923

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] Function of GPI-80 on prostate cancer cell line, PC3 cells2019

    • Author(s)
      Takeda Yuji, Kurota Yuta, Kato Tomoyuki, Araki Akemi, Saitoh Shinichi, and Asao Hironobu:
    • Organizer
      第48回日本免疫学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Myeloid cell heterogeneity indicating appearance of myeloid derived suppressor cells (MDSCs)in peripheral blood of metastatic renal cell carcinoma (mRCC)2019

    • Author(s)
      Tomoyuki Kato, Yuji Takeda, Yuta Kurota, Sei Naito, Hiromi Ito, Akemi Araki, Hironobu Asao, Norihiko Tsuchiya
    • Organizer
      ASCO GU-Genitourinary Cancers Symposium
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Analysis of urinary leukocytes during intravesical immunotherapy with BCG for non-muscle invasive bladder cancer2018

    • Author(s)
      Takeda Yuji, Kato Tomoyuki, Kurota Yuta, Ito Hiromi, Akemi Araki, Tsuchiya Norihiko, and Asao Hironobu
    • Organizer
      第77回日本癌学会
    • Related Report
      2018 Research-status Report
  • [Presentation] GPI-80, a useful marker of MDSC in mRCC patients, is a reference for the search for new MDSC markers2017

    • Author(s)
      Tomoyuki Kato, Yuji Takeda, Hitomi Ito, Yuta Kurota, Mayu Yagi, Toshihiko Sakurai, Sei Naito, Hisashi Kawazoe, Osamu Ichiyanagi, Norihiko Tsuchiya, Hironobu Asao
    • Organizer
      第76回日本癌学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 転移性腎細胞癌患者における末梢血中GPI-80発現は予後因子となりうる2017

    • Author(s)
      加藤智幸,武田裕司,伊藤裕美,黒田悠太,奈良英利,櫻井俊彦,西田隼人,内藤整,川添久,荒木明美,一柳統,浅尾裕信,土谷順彦
    • Organizer
      第55回日本癌治療学会学術集会
    • Related Report
      2017 Research-status Report
  • [Book] Mehods in Molecular Biology 1916, Pre-Clinical Models2019

    • Author(s)
      Takeda Y, Asao H, Wakabayashi I.
    • Total Pages
      343
    • Publisher
      Springer
    • ISBN
      9781493989935
    • Related Report
      2019 Annual Research Report
  • [Remarks] 山形大学医学部免疫学講座 武田裕司のページ

    • URL

      http://www.id.yamagata-u.ac.jp/Imm/h29-takeda/index.html

    • Related Report
      2019 Annual Research Report 2017 Research-status Report
  • [Remarks] 武田裕司の研究概要

    • URL

      http://www.id.yamagata-u.ac.jp/Imm/h29-takeda/index.html

    • Related Report
      2018 Research-status Report

URL: 

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

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