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Regulation of function of tumor-infiltrating myeloid cells by RNA adjuvant

Research Project

Project/Area Number 24590470
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Experimental pathology
Research InstitutionHokkaido University

Principal Investigator

SHIME Hiroaki  北海道大学, 医学(系)研究科(研究院), 助教 (70372133)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsがん免疫 / ミエロイド系細胞 / アジュバント / マクロファージ / TLR / MDSC / がん免疫療法 / 免疫抑制 / 自然免疫 / ミエロイド / 癌免疫療法 / 腫瘍随伴マクロファージ(TAM) / RNAアジュバント / 免疫抑制細胞 / IPS-1 MAVS / NK細胞 / インターフェロン
Outline of Final Research Achievements

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of cells that exhibit immunosuppressive activity in cancer. We have studied the effects of innate immune signaling activation on MDSC function. A double-stranded (ds) RNA adjuvant induced IFN-α production by MDSCs through MAVS (IPS-1) signaling pathway, leading to NK cell activation. dsRNA adjuvant stimulation also converted MDSCs into cells with anti-tumor activity through TICAM-1 (TRIF) signaling pathway. In contrast, Pam2 lipopeptide-induced toll-like receptor 2 (TLR2) activation resulted in enhanced survival and immunosuppressive activity of MDSCs. Thus, our data suggest that innate immune signaling is closely related to expansion and function of MDSCs.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (31 results)

All 2015 2014 2013 2012 Other

All Journal Article (14 results) (of which Peer Reviewed: 7 results,  Acknowledgement Compliant: 1 results) Presentation (13 results) Remarks (4 results)

  • [Journal Article] Pam2 lipopeptides systemically increase myeloid-derived suppressor cells through TLR2 signaling.2015

    • Author(s)
      Maruyama A, Shime H, Takeda Y, Azuma M, Matsumoto M, and Seya T
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 457 Issue: 3 Pages: 445-450

    • DOI

      10.1016/j.bbrc.2015.01.011

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Defined TLR3-specific adjuvant that induces NK and CTL activation without significant cytokine production in vivo.2015

    • Author(s)
      Matsumoto M, Tatematsu M, Nishikawa F, Azuma M, Ishii N, Morii-Sakai A, Shime H, Seya T
    • Journal Title

      Nature Communications

      Volume: 6 Issue: 1 Pages: 6280-6280

    • DOI

      10.1038/ncomms7280

    • NAID

      120005619610

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PolyI:C-induced, TLR3/RIP3-dependent necroptosis backs up immune effector-mediated tumor elimination in vivo.2015

    • Author(s)
      Takemura R, Takaki H, Okada S, Shime H, Oshiumi H, Akazawa T, Matsumoto M, Tejima T, and Seya T.
    • Journal Title

      Cancer Immunology Research

    • NAID

      120005820710

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The role of innate immune signaling in regulation of tumor-associated myeloid cells2015

    • Author(s)
      Shime H, Matsumoto M, Seya T
    • Journal Title

      Inflammation and immunity in cancer

      Pages: 25-47

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Myeloid-derived suppressor cells confer tumor-suppressive functions on natural killer cells via polyinosinic:polycytidylic acid treatment in mouse tumor model.2014

    • Author(s)
      Shime, H., A. Kojima, A. Maruyama, Y. Saito, H. Oshiumi, M. Matsumoto, and T. Seya.
    • Journal Title

      J. Innate. Immun.

      Volume: 6 Issue: 3 Pages: 293-305

    • DOI

      10.1159/000355126

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] dsRNAによるTAM, MDSCの腫瘍免疫抑制作用から活性化作用への変換2014

    • Author(s)
      志馬寛明、松本美佐子、瀬谷 司
    • Journal Title

      臨床免疫・アレルギー科

      Volume: 61 Pages: 613-620

    • Related Report
      2014 Annual Research Report
  • [Journal Article] 腫瘍浸潤マクロファージのRNA応答2014

    • Author(s)
      瀬谷 司、志馬寛明、松本美佐子
    • Journal Title

      細胞工学

      Volume: 33 Pages: 1242-1246

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Poly I:Cの刺激により活性化したミエロイド由来抑制性細胞はナチュラルキラー細胞に抗癌活性を付与する2014

    • Author(s)
      志馬寛明、児島絢子、丸山晃、斉藤祐介、押海裕之、松本美佐子、瀬谷 司
    • Journal Title

      北海道医学雑誌

      Volume: in press

    • Related Report
      2013 Research-status Report
  • [Journal Article] dsRNAによるTAM、MDSCの腫瘍免疫抑制作用から活性化作用への変換2014

    • Author(s)
      志馬寛明、松本美佐子、瀬谷 司
    • Journal Title

      臨床・免疫アレルギー科

      Volume: in press

    • Related Report
      2013 Research-status Report
  • [Journal Article] TLR3シグナル経路の活性化は腫瘍内ミエロイド系細胞を癌攻撃型エフェクターに転換する2013

    • Author(s)
      志馬寛明、松本美佐子、押海裕之、田中伸哉、中根明夫、岩倉洋一郎、田原秀晃、井上徳光、瀬谷 司
    • Journal Title

      北海道医学雑誌

      Volume: 88 Pages: 81-81

    • NAID

      10031165881

    • Related Report
      2013 Research-status Report
  • [Journal Article] Toll-like receptor (TLR)と制御性T細胞(Treg)2013

    • Author(s)
      志馬寛明、瀬谷 司
    • Journal Title

      週刊医学のあゆみ

      Volume: 246 Pages: 871-878

    • Related Report
      2013 Research-status Report
  • [Journal Article] Toll-like receptor 3 signaling converts tumor-supporting myeloid cells to tumoricidal effectors2012

    • Author(s)
      H.Shime
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 109 Issue: 6 Pages: 2066-2071

    • DOI

      10.1073/pnas.1113099109

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] TAMable tumor-associated macrophages in response to innate RNA sensing.2012

    • Author(s)
      Seya T, Shime H, Matsumoto M.
    • Journal Title

      Oncoimmunol.

      Volume: 1 Issue: 6 Pages: 1000-1001

    • DOI

      10.4161/onci.19894

    • NAID

      120005228653

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] TLR3/TICAM-1 signaling in tumor cell RIP3-dependent necroptosis.2012

    • Author(s)
      Seya T, Shime H, Takaki H, Azuma M, Oshiumi H, Matsumoto M.
    • Journal Title

      Oncoimmunol.

      Volume: 1 Issue: 6 Pages: 917-923

    • DOI

      10.4161/onci.21244

    • NAID

      120005228664

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] TICAM-1 signaling is essential for Ly6G+ cell-mediated inhibition of tumor growth induced by dsRNA adjuvant2014

    • Author(s)
      志馬寛明、松本美佐子、瀬谷 司
    • Organizer
      日本免疫学会
    • Place of Presentation
      国立京都国際会館(京都府・京都市)
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] Ly6G+ cell-mediated retardation of tumor growth in RNA adjuvant therapy2014

    • Author(s)
      志馬寛明、松本美佐子、瀬谷 司
    • Organizer
      日本癌学会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] TLR2 signal enhances survival and immune-suppressive activity of MDSCs2014

    • Author(s)
      丸山 晃、志馬寛明、松本美佐子、瀬谷 司
    • Organizer
      日本癌学会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] RNAアジュバントによるLy6G陽性細胞を介した抗がん作用2014

    • Author(s)
      志馬寛明、松本美佐子、瀬谷 司
    • Organizer
      日本がん免疫学会
    • Place of Presentation
      ひめぎんホール(愛媛県・松山市)
    • Year and Date
      2014-07-30 – 2014-08-01
    • Related Report
      2014 Annual Research Report
  • [Presentation] RNAアジュバントによる腫瘍随伴ミエロイド系細胞を介した抗癌作用2014

    • Author(s)
      志馬 寛明、松本 美佐子、瀬谷 司
    • Organizer
      がん研究分野の特性等を踏まえた支援活動公開シンポジウム
    • Place of Presentation
      東京(一橋講堂)
    • Related Report
      2013 Research-status Report
  • [Presentation] dsRNA adjuvant induces the antitumor function of tumor-associated myeloid cells.2014

    • Author(s)
      Shime H, Matsumoto M, Seya T
    • Organizer
      4th International symposium on carcinogenic spiral
    • Place of Presentation
      札幌(京王プラザホテル)
    • Related Report
      2013 Research-status Report
  • [Presentation] Supportive involvement of tumor-associated myeloid cells in RNA adjuvant therapy for cancer.2013

    • Author(s)
      Shime H, Matsumoto M, Oshiumi H, Seya T
    • Organizer
      ICI2013
    • Place of Presentation
      ミラノ(MiCo)
    • Related Report
      2013 Research-status Report
  • [Presentation] RNAアジュバントによる腫瘍内マクロファージの機能転換を介した新規抗腫瘍作用2013

    • Author(s)
      志馬寛明、松本美佐子、押海裕之、瀬谷司
    • Organizer
      「がん研究分野の特性等を踏まえた支援活動」 公開シンポジウム
    • Place of Presentation
      学術総合センター 一橋記念講堂(東京都)
    • Related Report
      2012 Research-status Report
  • [Presentation] 担癌宿主で増加するCD11b+Gr1+細胞は2本鎖RNAの投与によりNK細胞活性化能を獲得する2012

    • Author(s)
      志馬 寛明、児島 絢子、松本 美佐子、瀬谷 司
    • Organizer
      日本がん免疫学会
    • Place of Presentation
      北海道大学(札幌)
    • Related Report
      2012 Research-status Report
  • [Presentation] The role of tumor-associated myeloid cells in RNA adjuvant therapy2012

    • Author(s)
      Hiroaki SHIME, Misako MATSUMOTO, Tsukasa SEYA
    • Organizer
      日本癌学会
    • Place of Presentation
      札幌市教育文化会館(北海道)
    • Related Report
      2012 Research-status Report
  • [Presentation] A crucial RNA adjuvant for immunotherapy for cancer2012

    • Author(s)
      Tsukasa Seya, Misako Matsumoto, Hiroaki Shime, Masahiro Azuma
    • Organizer
      日本癌学会
    • Place of Presentation
      さっぽろ芸文館(北海道)
    • Related Report
      2012 Research-status Report
  • [Presentation] NK cell activation by tumor-associated myeloid cells during RNA adjuvant therapy for cancer2012

    • Author(s)
      Hiroaki SHIME, Misako MATSUMOTO, Tsukasa SEYA
    • Organizer
      IEIIS2012
    • Place of Presentation
      学術総合センター 一橋記念講堂(東京都)
    • Related Report
      2012 Research-status Report
  • [Presentation] Splenic CD11b+Gr1+ cells turn NK activators by dsRNA in tumor-implant mice2012

    • Author(s)
      Hiroaki SHIME, Misako MATSUMOTO, Tsukasa SEYA
    • Organizer
      日本免疫学会
    • Place of Presentation
      神戸国際展示場(兵庫県)
    • Related Report
      2012 Research-status Report
  • [Remarks] 北海道大学医学研究科免疫学分野

    • URL

      http://www.hucc.hokudai.ac.jp/~e20536/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] 北海道大学医学研究科免疫学分野ホームページ

    • URL

      http://www.hucc.hokudai.ac.jp/~e20536/

    • Related Report
      2013 Research-status Report
  • [Remarks] 北海道大学大学院医学研究科免疫学分野

    • URL

      http://www.hucc.hokudai.ac.jp/~e20536/

    • Related Report
      2012 Research-status Report
  • [Remarks] 悪玉の腫瘍内マクロファージを善玉に変えてがんを治す試みに成功

    • URL

      http://www.hokudai.ac.jp/bureau/topics/press_release/120117_pr_med.pdf

    • Related Report
      2012 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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