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

Abstract

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.

• Authors: Maya Eisenring, Johannes vom Berg, Glen Kristiansen, Elisabeth Saller, Burkhard Becher
• Journal: Nature immunology (Nat Immunol) Vol. 11 Issue 11 Pg. 1030-8 (Nov 2010) ISSN: 1529-2916 [Electronic] United States
• PMID: 20935648 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• 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