Interleukin-12 activates NK cells for IFN-gamma -dependent and NKT cells for IFN-gamma -independent antimetastatic activity

Hafner, M. and Falk, Werner and Echtenacher, B. and Maennel, Daniela N. (1999) Interleukin-12 activates NK cells for IFN-gamma -dependent and NKT cells for IFN-gamma -independent antimetastatic activity. EUROPEAN CYTOKINE NETWORK, 10 (4). pp. 541-548. ISSN 1148-5493,

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Abstract

Mechanisms involved in the antimetastatic effect of IL-12 were analyzed in a mouse model of experimental metastasis with either syngeneic fibrosarcoma cells colonizing the lungs or syngeneic B cell lymphoma cells colonizing the liver. IL-12 pretreatment effectively reduced the number of tumor colonies in both systems. This effect was already manifest 24 hours after tumor cell injection, indicating a T and B cell-independent mechanism. Therefore, the involvement of NK and alpha beta NKT cells was investigated using mice with defective NK and alpha beta NKT cell functions. Mice with impaired NK functions due to NK cell depletion, were less responsive to the antimetastatic IL-12 effect. IL-12 treatment failed to inhibit metastasis in beta(2)-microglobulin-deficient mice which lack alpha beta NKT cells in addition to having impaired NK cell activity, thus, demonstrating the functional importance of IL-12-activated NK and alpha beta NKT cells. While the IL-12-induced antimetastatic effect of NK cells was dependent on IFN-gamma action, IL-12 activation of alpha beta NKT cells did not involve IFN-gamma. The neutralization of IFN-gamma or the use of IFN-gamma receptor-deficient mice did not alter the IL-12-induced effect in the absence of NK cells. Activation of effector cells of the innate immune system, such as NK and alpha beta NKT cells, seems to be the main mechanism for the antimetastatic effect of IL-12.

Item Type: Article
Uncontrolled Keywords: BETA T-CELLS; TUMOR-NECROSIS-FACTOR; NATURAL-KILLER-CELLS; IN-VIVO; INTERFERON-GAMMA; MONOCLONAL-ANTIBODY; RECOMBINANT IL-12; BONE-MARROW; MICE; METASTASIS; cytokines; NK cells; tumor immunity; in vivo animal models; metastasis
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 06 Dec 2022 11:06
Last Modified: 06 Dec 2022 11:06
URI: https://pred.uni-regensburg.de/id/eprint/48780

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