DC therapy induces long-term NK reactivity to tumors via host DC

Eur J Immunol. 2009 Feb;39(2):457-68. doi: 10.1002/eji.200838794.


We vaccinated mice with DC loaded with or without invariant NKT-cell ligand alpha-galactosylceramide and evaluated long-term resistance against tumor challenge. When mice had been given either DC or DC/galactosylceramide and were challenged with tumor cells even 6-12 months later, both NK and NKT cells were quickly activated to express CD69 and produce IFN-gamma. The NK cells could resist a challenge with several different tumors in vivo. The activated NK and NKT cells could be depleted with anti-NK1.1 treatment. In spite of this, the activated cells recovered, indicating that tumor-responsive NK and NKT cells were being generated continuously as a result of vaccination with DC and were not true memory cells. The NK and NKT antitumor response in DC-vaccinated mice depended on CD4(+) T cells, but neither CD8(+)T cells nor CD4(+)CD25(+) regulatory T cells. However, both vaccine DC and host DC were required for the development of long-term, tumor reactive innate immunity. These results indicate that DC therapy in mice induces long-lasting innate NK- and NKT-cell activation through a pathway that requires host DC and CD4(+) T cells and that the continued generation of active NK cells resists the establishment of metastases in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Cell Line, Tumor
  • Dendritic Cells / immunology
  • Dendritic Cells / transplantation*
  • Female
  • Galactosylceramides / immunology
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / metabolism
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / therapy*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Natural Killer T-Cells / immunology*
  • Natural Killer T-Cells / metabolism


  • Cancer Vaccines
  • Galactosylceramides
  • alpha-galactosylceramide
  • Interferon-gamma