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腫瘍の免疫逃避分子メカニズムの解明と制御

Publicly Offered Research

Project AreaImmunological Self Recognition and its Disorders
Project/Area Number 22021006
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionUniversity of Tsukuba

Principal Investigator

渋谷 和子  筑波大学, 医学医療系, 准教授 (00302406)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥9,800,000 (Direct Cost: ¥9,800,000)
Fiscal Year 2011: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2010: ¥4,900,000 (Direct Cost: ¥4,900,000)
Keywords免疫学 / 免疫学監視 / 免疫逃避 / 免疫制御 / 可溶型CD155
Research Abstract

がんの発症には、免疫監視と免疫逃避のバランスが重要であると考えられている。しかし、その分子メカニズムの全貌はいまだ明らかではない。ヒトCD155は、ポリオウイルスレセプターとして同定された分子である。私達はこれまでにCD155のマウスホモログを同定し、ヒトCD155とマウスCD155が、それぞれ免疫系受容体のヒトDNAM-1とマウスDNAM-1のリガンドであることを見いだした。また、私達は、T細胞やNK細胞に細胞傷害活性を惹起するDNAM-1が腫瘍に発現する膜型CD155を認識することによって、免疫システムががんを排除することを明らかにした。一方、CD155にはバリアントの可溶型も存在する。がん患者の血清中の可溶型CD155値を観察すると、ステージの高いがん患者において可溶型CD155値が高い傾向にあった。可溶型CD155もDNAM-1と結合することから、可溶型CD155は膜型CD155のアンタゴニストとして機能し、腫瘍が免疫システムから逃避することに関与している可能性が考えられた。このことを確認するために、私達は、可溶型CD155を強制発現させた腫瘍株を樹立した。この可溶型CD155を産生する腫瘍株は、Mock腫瘍株と比較して、それ自体に増殖能の差を認めなかった。しかし、野生型マウスの生体内に移入すると、Mock腫瘍株は全匹において拒絶されたが、可溶型CD155を産生する腫瘍株は、DNAM-1免疫監視下にもかかわらず、全匹において腫瘍が拒絶されずに、急速に増大することが観察された。一方、免疫不全マウス(SCIDマウス)やDNAM-1遺伝子欠損マウスの生体内に移入した場合は、可溶型CD155産生腫瘍株とMock腫瘍株の増殖速度に差は認められなかった。以上の結果より、腫瘍より産生される可溶型CD155がDNAM-1による免疫監視システムからの逃避に関与していることが示された。

Report

(2 results)
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (30 results)

All 2012 2011 2010 Other

All Journal Article (8 results) (of which Peer Reviewed: 6 results) Presentation (20 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Identification of phosphatidylserine as a ligand for the CD300a immunoreceptor2012

    • Author(s)
      Chigusa Nakahashi-Oda, et.al.
    • Journal Title

      BBRC

      Volume: 417 Issue: 1 Pages: 646-650

    • DOI

      10.1016/j.bbrc.2011.12.025

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isolation and characterization of naive follicular dendritic cells2012

    • Author(s)
      Kenta Usui
    • Journal Title

      Molecular Immunology

      Volume: 50 Issue: 3 Pages: 172-176

    • DOI

      10.1016/j.molimm.2011.11.010

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The immunoreceptor adapter protein DAP12 suppresses B lymphocyte-driven adaptive immune responses2011

    • Author(s)
      Takako Nakano-Yokomizo, et.al.
    • Journal Title

      J Exp Med

      Volume: 8 Issue: 8 Pages: 1661-1671

    • DOI

      10.1084/jem.20101623

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reply to Seth et al.: DNAX accessory molecule-1 (DNAM-1) plays an important role in alloreactive CD8^+ T cells responsible for the exacerbation of acute graft-versus-host disease.2011

    • Author(s)
      Nabekura T, et.al.
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Critical role of DNAX accessory molecule-1 (DNAM-1) in the development of acute graft-versus-host disease in mice.2010

    • Author(s)
      Nabekura T, et.al.
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 107 Pages: 18593-18598

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An immunoglobulin-like receptor, Allergin-1, inhibits immunoglobulin E-mediated immediate hypersensitivity reactions.2010

    • Author(s)
      Hitomi K, et.al.
    • Journal Title

      Nature Immunology

      Volume: 11 Pages: 601-607

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ナチュラルキラー細胞2010

    • Author(s)
      鍋倉宰
    • Journal Title

      侵襲と免疫

      Volume: 19 Pages: 17-25

    • Related Report
      2010 Annual Research Report
  • [Journal Article] DNAM-1分子によるNK細胞の活性化2010

    • Author(s)
      鍋倉宰
    • Journal Title

      臨床免疫・アレルギー

      Volume: 53 Pages: 119-125

    • Related Report
      2010 Annual Research Report
  • [Presentation] Innate immune response receptors2012

    • Author(s)
      戸塚直也
    • Organizer
      World Immune Regulation Meeting-VI
    • Place of Presentation
      Zurich, Switzerland
    • Year and Date
      2012-03-20
    • Related Report
      2011 Annual Research Report
  • [Presentation] An immunoglobulin-like receptor, Allergin-1, inhibits immunoglobulin E-mediated immediate hypersensitivity reactions2011

    • Author(s)
      田原聡子
    • Organizer
      第40回日本免疫学会
    • Place of Presentation
      幕張メッセ
    • Year and Date
      2011-11-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] MAIR-II (CD300d) on Ly-6Chigh inflammatory monocytes plays a crucial role in inflammatory responses in a murine sepsis model2011

    • Author(s)
      戸塚直也
    • Organizer
      第40回日本免疫学会
    • Place of Presentation
      幕張メッセ
    • Year and Date
      2011-11-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] ナイーブマウス牌臓からのFDCの単離2011

    • Author(s)
      臼井健太
    • Organizer
      第40回日本免疫学会
    • Place of Presentation
      幕張メッセ
    • Year and Date
      2011-11-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] Iga/IgM受容体、Fcα/μ受容体の二量体形成の解析2011

    • Author(s)
      高垣香那
    • Organizer
      第40回日本免疫学会
    • Place of Presentation
      幕張メッセ
    • Year and Date
      2011-11-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] An immunoreceptor adapter protein, DAP12, suppresses adaptive immune responses mediated by B lymphocytes2011

    • Author(s)
      小田ちぐさ
    • Organizer
      第40回日本免疫学会
    • Place of Presentation
      幕張メッセ
    • Year and Date
      2011-11-27
    • Related Report
      2011 Annual Research Report
  • [Presentation] The role of CD155, a noval co-stimulatory molecule in CD4+ T cell, in contact dermatitis2011

    • Author(s)
      山下由美
    • Organizer
      第40回日本免疫学会
    • Place of Presentation
      幕張メッセ
    • Year and Date
      2011-11-27
    • Related Report
      2011 Annual Research Report
  • [Presentation] Crinical role of DNAM-1 in the development of acute GVHD2011

    • Author(s)
      渋谷彰
    • Organizer
      第73回日本血液学会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2011-10-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] 急性移植片対宿主病の予知診断法と分子標的療法の開発2011

    • Author(s)
      金谷穣
    • Organizer
      第3回造血器腫瘍免疫療法研究会
    • Place of Presentation
      別府ホテル白菊
    • Year and Date
      2011-08-20
    • Related Report
      2011 Annual Research Report
  • [Presentation] Critical role of DNAM-1 in the development of acute graft-versus-host disease in mice2010

    • Author(s)
      Kazuko SHIBUYA
    • Organizer
      2010 Symposium for "Cutting edge of immunology ; innate immunity and immune regulation"
    • Place of Presentation
      Hitotsubashi Memorial Hall (Tokyo)
    • Year and Date
      2010-12-03
    • Related Report
      2010 Annual Research Report
  • [Presentation] 抗DNAM 1モノクローナル抗体を用いた移植片対宿主病に対する新規予防および治療法の開発2010

    • Author(s)
      鍋倉宰
    • Organizer
      第2回造血器腫瘍免疫療法研究会
    • Place of Presentation
      愛媛大和屋本店
    • Year and Date
      2010-08-28
    • Related Report
      2010 Annual Research Report
  • [Presentation] Regulation of serum IgA production by the Fcα/μ, an Fc receptor for IgA and IgM2010

    • Author(s)
      Shin-ichiro Honda
    • Organizer
      第14回国際免疫学会議
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2010-08-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] A critical role of DNAM-1 in the development of acute graft-versus-host disease2010

    • Author(s)
      Tsukasa Nabekura
    • Organizer
      第14回国際免疫学会議
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2010-08-26
    • Related Report
      2010 Annual Research Report
  • [Presentation] Requirement of cytoplasmic portion for dimer formation of Fcα/μ receptor expresscd on cell surface2010

    • Author(s)
      Yukiko Cho
    • Organizer
      第14回国際免疫学会議
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2010-08-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] MAIR-□(CD300d)plays a crucial role in inflammatory responses in a murine sepsis model2010

    • Author(s)
      Naoya Totsuka
    • Organizer
      第14回国際免疫学会議
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2010-08-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] An immunoreceptor ando adaptor complex, MAIR-□/DAP12, negatively regulates B cell proliferation2010

    • Author(s)
      Takako Nakano
    • Organizer
      第14回国際免疫学会議
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2010-08-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] Decreased mortality in MAIR-□(CD300a)-deficient mice with experimental sepsis induced by cecal ligation and puncture2010

    • Author(s)
      Chigusa Nakahashi-Oda
    • Organizer
      第14回国際免疫学会議
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2010-08-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] A novel immunoglobulin-like receptor, Allergin-1, inhibits IgE-mediated allergic responses2010

    • Author(s)
      Kaori Hitomi
    • Organizer
      第14回国際免疫学会議
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2010-08-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] Identification and characterization of the poliovirus receptor (CD155) as a novel co-stimulatory molecule in CD4+ T cells2010

    • Author(s)
      Yumi Yamashita
    • Organizer
      第14回国際免疫学会議
    • Place of Presentation
      神戸ポートピアホテル
    • Related Report
      2010 Annual Research Report
  • [Presentation] A novel immunoglobulin-like receptor, Allergin-1, inhibits IgE-mediated allergic responses2010

    • Author(s)
      Satoko Tahara-Hanaoka
    • Organizer
      CSHL Meeting-Gene Expression & Signaling in the Immune System
    • Place of Presentation
      New York, USA
    • Related Report
      2010 Annual Research Report
  • [Remarks] リポジトリ論文URL

    • URL

      http://www.tulips.tsukuba.ac.jp/dspace/handle/2241/101766/

    • Related Report
      2010 Annual Research Report
  • [Patent(Industrial Property Rights)] 臓器移植拒絶予防法の開発2012

    • Inventor(s)
      渋谷彰、渋谷和子、阿部史枝
    • Industrial Property Rights Holder
      筑波大学
    • Industrial Property Number
      2011-000094
    • Filing Date
      2012-01-31
    • Related Report
      2011 Annual Research Report

URL: 

Published: 2010-08-23   Modified: 2018-03-28  

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