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Clearance of Dead Tumor Cells and Tumor Immunity

Research Project

Project/Area Number 21790396
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionTokyo University of Pharmacy and Life Science (2011)
The Institute of Physical and Chemical Research (2009-2010)

Principal Investigator

ASANO Kenichi  東京薬科大学, 生命科学部, 准教授 (10513400)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywords腫瘍 / リンパ節 / CD169 / マクロファージ / 死細胞 / クロスプレゼンテーション / 免疫寛容 / 貪食
Research Abstract

Tumor cells are considered' altered self' because they accumulate genetic mutations and acquire features that enable them to evade immune surveillance. The generation of tumor-directed cytotoxic T lymphocytes is considered crucial for the induction of anti-tumor immunity. To activate these CD8 T cells, antigen presenting cells(APCs) must initially acquire tumor cell-associated antigens. The major source of tumor antigens is dead tumor cells, but little is known about how APCs in draining lymph nodes acquire and crosspresent these antigens. Here we show that CD169^+macrophages phagocytose dead tumor cells transported via lymphatic flow and subsequently crossprime CD8 T cells. Subcutaneous immunization with irradiated tumor cells protects mice from syngenic tumor. However, tumor antigen-specific CD8 T cell activation and subsequent anti-tumor immunity are severely impaired in mice depleted with CD169^+macrophages. Neither migratory dendritic cells(DCs) nor lymph node-resident conventional DCs are essential for the crosspresentation of tumor antigens. Thus, we have identified lymph node CD169^+macrophages as a novel APC subset dominating early activation of tumor antigen-specific CD8 T cells.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (8 results)

All 2011 2010

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

  • [Journal Article]2011

    • Author(s)
      Asano K, Nabeyama A, Miyake Y, et al.
    • Journal Title

      Immunity

      Volume: 34 Pages: 85-95

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] CD169-positive macrophages dominate antitumor immunity by crosspresenting dead cell-associated antigens.2011

    • Author(s)
      Asano, Kenichi
    • Journal Title

      Immunity

      Volume: 34 Pages: 85-95

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immune regulation by apoptotic cell clearance.2010

    • Author(s)
      Tanaka, Masato
    • Journal Title

      Annals of New York Academy of Sciences

      Volume: 1209 Pages: 37-42

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] xCT deficiency accelerates chemically induced tumorigenesis.2010

    • Author(s)
      Nabeyama, Ami
    • Journal Title

      Proceedings of National Academy of Sciences of the United States of America

      Volume: 107 Pages: 6436-6441

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Role of CD169+Macrophages in the Crosspresentation of Cell-associated Antigens2010

    • Organizer
      14^<th> International Congress of Immunology
    • Place of Presentation
      Kobe, Japan
    • Year and Date
      2010-08-25
    • Related Report
      2011 Final Research Report
  • [Presentation] Role of CD169+ macrophages in the crosspresentation of cell-associated antigens.2010

    • Author(s)
      Asano, Kenichi
    • Organizer
      International Congress of Immunology
    • Place of Presentation
      Kobe, Japan
    • Year and Date
      2010-08-25
    • Related Report
      2010 Annual Research Report
  • [Presentation] Macrophages dictate the direction of immune response against dead cell-associated antigens.2010

    • Author(s)
      Asano, Kenichi
    • Organizer
      Annual World Congress of Immunodiseases and Therapy
    • Place of Presentation
      Beijing, China
    • Year and Date
      2010-05-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] Macrophages Dictate the Direction of Immune response against Dead Cell-associated Antigens2010

    • Organizer
      BIT's 1^<st> Annual World Congress of Immunodiseases and Therapy
    • Place of Presentation
      Beijing, China
    • Related Report
      2011 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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