CD169-positive macrophages dominate antitumor immunity by crosspresenting dead cell-associated antigens

Immunity. 2011 Jan 28;34(1):85-95. doi: 10.1016/j.immuni.2010.12.011. Epub 2010 Dec 30.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / immunology
  • CD11c Antigen / biosynthesis
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism*
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Movement / immunology
  • Cross-Priming
  • Immunization
  • Lymph Nodes / pathology*
  • Lymphocyte Activation
  • Lymphoma, T-Cell / immunology*
  • Lymphoma, T-Cell / pathology
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Macrophages / pathology
  • Membrane Glycoproteins / biosynthesis*
  • Mice
  • Mice, Transgenic
  • Phagocytosis / immunology
  • Receptors, Immunologic / biosynthesis*
  • Sialic Acid Binding Ig-like Lectin 1


  • Antigens, Neoplasm
  • CD11c Antigen
  • Membrane Glycoproteins
  • Receptors, Immunologic
  • Sialic Acid Binding Ig-like Lectin 1
  • Siglec1 protein, mouse