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


Eisenring, M; vom Berg, J; Kristiansen, G; Saller, E; Becher, B (2010). IL-12 initiates tumor rejection via lymphoid tissue-inducer cells bearing the natural cytotoxicity receptor NKp46. Nature Immunology, 11(11):1030-1038.

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.

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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Surgical Pathology
04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2010
Deposited On:13 Jan 2011 13:12
Last Modified:05 Apr 2016 14:27
Publisher:Nature Publishing Group
ISSN:1529-2908
Publisher DOI:10.1038/ni.1947
PubMed ID:20935648
Permanent URL: http://doi.org/10.5167/uzh-39908

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