IL-12 initiates tumor rejection via lymphoid tissue-inducer cells bearing the natural cytotoxicity receptor NKp46

Nat Immunol. 2010 Nov;11(11):1030-8. doi: 10.1038/ni.1947. Epub 2010 Oct 10.


The potent tumoricidal activity of interleukin 12 (IL-12) is thought to be mediated by the activation and polarization of natural killer (NK) cells and T helper type 1 (T(H)1) cells, respectively. By systematic analysis of the IL-12-induced immune response to subcutaneous melanoma (B16), we found that tumor suppression was mediated independently of T lymphocytes or NK cells. IL-12 initiated local antitumor immunity by stimulating a subset of NKp46(+) lymphoid tissue-inducer (LTi) cells dependent on the transcription factor RORγt. The presence of these NKp46(+) LTi cells induced upregulation of adhesion molecules in the tumor vasculature and resulted in more leukocyte invasion. Thus, this innate cell type is responsive to IL-12 and is a powerful mediator of tumor suppression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Interleukin-12 / immunology*
  • Lymphoid Tissue / immunology*
  • Melanoma / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Natural Cytotoxicity Triggering Receptor 1 / immunology*
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Tumor Cells, Cultured


  • Natural Cytotoxicity Triggering Receptor 1
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • Interleukin-12