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Cell Rep. 2014 Oct 9;9(1):90-103. doi: 10.1016/j.celrep.2014.08.049. Epub 2014 Sep 25.

NF-κB functions in tumor initiation by suppressing the surveillance of both innate and adaptive immune cells.

Author information

1
Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA; Department of Internal Medicine, Arthur G. James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
2
Molecular, Cellular and Developmental Biology Graduate Program, The Ohio State University, Columbus, OH 43210, USA.
3
Department of Internal Medicine, Arthur G. James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
4
Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA; Molecular, Cellular and Developmental Biology Graduate Program, The Ohio State University, Columbus, OH 43210, USA; Department of Internal Medicine, Arthur G. James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA. Electronic address: denis.guttridge@osumc.edu.

Abstract

NF-κB is considered a major contributor to tumor development, but how this factor functions in the initial stages of oncogenesis is not clear. In a model of Ras-induced transformation, we probed NF-κB function as preneoplastic cells formed tumors in mice. As previously shown, the p65 subunit of NF-κB acts as a tumor suppressor in normal cells by sustaining senescence following DNA damage. Our current data reveal that, following immortalization, p65 switches to an oncogene by counteracting the surveillance properties of immune cells. NF-κB exerts this effect by protecting transformed cells against macrophage-derived proapoptotic factors, tumor necrosis factor, and nitric oxide. Additionally, NF-κB acts through transforming growth factor beta (TGF-β) to mitigate T cell cytotoxicity and other factors to expand myeloid-derived suppressor cells. Together, these data suggest that NF-κB functions in the early stages of transformation by suppressing immune surveillance of both innate and adaptive immune cells, information that may be useful for targeted immunotherapies.

PMID:
25263557
PMCID:
PMC4882153
DOI:
10.1016/j.celrep.2014.08.049
[Indexed for MEDLINE]
Free PMC Article

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