A novel dendritic cell subset involved in tumor immunosurveillance

Nat Med. 2006 Feb;12(2):214-9. doi: 10.1038/nm1356. Epub 2006 Jan 29.


The interferon (IFN)-gamma-induced TRAIL effector mechanism is a vital component of cancer immunosurveillance by natural killer (NK) cells in mice. Here we show that the main source of IFN-gamma is not the conventional NK cell but a subset of B220(+)Ly6C(-) dendritic cells, which are atypical insofar as they express NK cell-surface molecules. Upon contact with a variety of tumor cells that are poorly recognized by NK cells, B220(+)NK1.1(+) dendritic cells secrete high levels of IFN-gamma and mediate TRAIL-dependent lysis of tumor cells. Adoptive transfer of these IFN-producing killer dendritic cells (IKDCs) into tumor-bearing Rag2(-/-)Il2rg(-/-) mice prevented tumor outgrowth, whereas transfer of conventional NK cells did not. In conclusion, we identified IKDCs as pivotal sensors and effectors of the innate antitumor immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigen Presentation
  • Antigens, Ly
  • Antigens, Surface / metabolism
  • Apoptosis Regulatory Proteins / immunology
  • CD11c Antigen / metabolism
  • Cell Line, Tumor
  • Cytotoxicity, Immunologic
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / genetics
  • Dendritic Cells / classification*
  • Dendritic Cells / immunology*
  • Dendritic Cells / ultrastructure
  • Female
  • Interferon-gamma / biosynthesis
  • Interleukin Receptor Common gamma Subunit
  • Killer Cells, Natural / immunology
  • Lectins, C-Type / metabolism
  • Leukocyte Common Antigens / metabolism
  • Membrane Glycoproteins / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Nude
  • Microscopy, Electron
  • NK Cell Lectin-Like Receptor Subfamily B
  • Neoplasms, Experimental / immunology*
  • Receptors, Interleukin / deficiency
  • Receptors, Interleukin / genetics
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor-alpha / immunology


  • Antigens, Ly
  • Antigens, Surface
  • Apoptosis Regulatory Proteins
  • CD11c Antigen
  • DNA-Binding Proteins
  • Il2rg protein, mouse
  • Interleukin Receptor Common gamma Subunit
  • Klrb1c protein, mouse
  • Lectins, C-Type
  • Membrane Glycoproteins
  • NK Cell Lectin-Like Receptor Subfamily B
  • Rag2 protein, mouse
  • Receptors, Interleukin
  • TNF-Related Apoptosis-Inducing Ligand
  • Tnfsf10 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Leukocyte Common Antigens