Immunity
Volume 34, Issue 1, 28 January 2011, Pages 85-95
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Article
CD169-Positive Macrophages Dominate Antitumor Immunity by Crosspresenting Dead Cell-Associated Antigens

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Summary

The generation of tumor-directed cytotoxic T lymphocytes is considered crucial for the induction of antitumor 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 crosspresent tumor antigens to CD8+ T cells. Subcutaneous immunization with irradiated tumor cells protects mice from syngenic tumor. However, tumor antigen-specific CD8+ T cell activation and subsequent antitumor 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 CD169+ macrophages as lymph node-resident APCs dominating early activation of tumor antigen-specific CD8+ T cells.

Highlights

► Dead tumor cells in periphery accumulate in the draining lymph node sinus ► CD169+ macrophages phagocytose and crosspresent dead cell-associated antigens ► CD169+ macrophage-depleted mice fail to crossprime tumor-specific CD8 T cells ► CD169+ macrophages link tumor cell death and induction of antitumor immunity

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