2011 Fiscal Year Final Research Report
Clearance of Dead Tumor Cells and Tumor Immunity
| Project/Area Number |
21790396
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Tokyo University of Pharmacy and Life Science (2011)
The Institute of Physical and Chemical Research (2009-2010) |
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Principal Investigator |
ASANO Kenichi 東京薬科大学, 生命科学部, 准教授 (10513400)
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| Project Period (FY) |
2009 – 2011
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| 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 |
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| 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.
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