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Int. J. Mol. Sci. 2015, 16(2), 4343-4361; doi:10.3390/ijms16024343

Metastatic Melanoma Cells Evade Immune Detection by Silencing STAT1

Division of Cellular Biology and Immunology, Department of Biology, Georgia State University, Atlanta, GA 30303, USA
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Author to whom correspondence should be addressed.
Academic Editor: Terrence Piva
Received: 25 November 2014 / Accepted: 11 February 2015 / Published: 17 February 2015
(This article belongs to the Section Biochemistry, Molecular and Cellular Biology)
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Abstract

Transcriptional activation of major histocompatibility complex (MHC) I and II molecules by the cytokine, interferon γ (IFN-γ), is a key step in cell-mediated immunity against pathogens and tumors. Recent evidence suggests that suppression of MHC I and II expression on multiple tumor types plays important roles in tumor immunoevasion. One such tumor is malignant melanoma, a leading cause of skin cancer-related deaths. Despite growing awareness of MHC expression defects, the molecular mechanisms by which melanoma cells suppress MHC and escape from immune-mediated elimination remain unknown. Here, we analyze the dysregulation of the Janus kinase (JAK)/STAT pathway and its role in the suppression of MHC II in melanoma cell lines at the radial growth phase (RGP), the vertical growth phase (VGP) and the metastatic phase (MET). While RGP and VGP cells both express MHC II, MET cells lack not only MHC II, but also the critical transcription factors, interferon response factor (IRF) 1 and its upstream activator, signal transducer and activator of transcription 1 (STAT1). Suppression of STAT1 in vitro was also observed in patient tumor samples, suggesting STAT1 silencing as a global mechanism of MHC II suppression and immunoevasion. View Full-Text
Keywords: MHC II; melanoma; STAT1; immunosurveillance MHC II; melanoma; STAT1; immunosurveillance
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Osborn, J.L.; Greer, S.F. Metastatic Melanoma Cells Evade Immune Detection by Silencing STAT1. Int. J. Mol. Sci. 2015, 16, 4343-4361.

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