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Cytokine. 2009 Sep;47(3):199-205. doi: 10.1016/j.cyto.2009.06.006. Epub 2009 Jul 28.

Human cancer cells have specifically lost the ability to induce the synergistic state caused by tumor necrosis factor plus interferon-beta.

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Department of Molecular Genetics and Microbiology, College of Medicine, University of Florida, 1600 SW Archer Road, R4-295, Gainesville, FL 32610, USA.


Tumor necrosis factor (TNF) and the members of the interferon (IFN) family are major inducible cytokines that function to counteract viral infections or cellular transformation. Recently, our lab has characterized a novel antiviral state which is induced in primary human fibroblasts by co-treatment with TNF plus IFNbeta. Here, we demonstrate that this synergistic state is both antiviral and cytostatic for primary human cells. Significantly, we observed that a wide spectrum of transformed human cancer cells have universally lost the ability to induce the TNF/IFNbeta synergistic state, as defined by three separate criteria. We hypothesize that the ability to induce the TNF/IFNbeta synergistic state is a unique feature of primary cells and is incompatible with cellular immortalization and/or transformation.

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