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dc.contributor.authorWu, Jennifer D.en_US
dc.contributor.authorHiggins, Lily M.en_US
dc.contributor.authorSteinle, Alexanderen_US
dc.contributor.authorCosman, Daviden_US
dc.contributor.authorHaugk, Kathyen_US
dc.contributor.authorPlymate, Stephen R.en_US
dc.date.accessioned2010-05-06T20:10:17Z
dc.date.available2010-05-06T20:10:17Z
dc.date.issued2004-08-16en_US
dc.identifier.citationWu JD, Higgins LM, Steinle A, et al. Prevalent expression of the immunostimulatory MHC class I chain–related molecule is counteracted by shedding in prostate cancer. J Clin Invest. 2004;114(4):560-568.en_US
dc.identifier.other10.1172/JCI22206en_US
dc.identifier.urihttp://www.jci.org/articles/view/22206en_US
dc.identifier.urihttp://hdl.handle.net/1773/15883
dc.description.abstractThe MHC class I chain–related molecules (MICs) have previously been shown to be induced on most epithelial tumor cells. Engagement of MIC by the activating immune receptor NKG2D triggers NK cells and augments antigen-specific CTL anti-tumor immunity. The MIC-NKG2D system was proposed to participate in epithelial tumor immune surveillance. Paradoxically, studies suggest that tumors may evade MIC-NKG2D–mediated immunity by MIC shedding–induced impairment of effector cell function. Here we demonstrate the first evidence to our knowledge of a significant correlation of MIC shedding and deficiency in NK cell function with the grade of disease in prostate cancer. MIC is widely expressed in prostate carcinoma. The presence of surface target MIC, however, is counteracted by shedding. A significant increase in serum levels of soluble MIC (sMIC) and deficiency in NK cell function was shown in patients with advanced cancer. Finally, the deficiency in NK cell function can be overcome by treatment with IL-2 or IL-15 in vitro. Our results suggest that (a) deficiency in MIC-NKG2D immune surveillance may contribute to prostate cancer progression, (b) sMIC may be a novel biomarker for prostate cancer, and (c) using cytokines to restore MIC-NKG2D–mediated immunity may have clinical significance for prostate cancer in cell-based adaptive immunotherapy.en_US
dc.description.sponsorshipNIH grants RO1DK52683 and PO1 CA85859 and a Department of Veterans Affairs Research Service Award to S.R. Plymate and Department of Defense New Investigator’s Award W81XWH-04-1-0577 to J.D. Wu.en_US
dc.language.isoen_USen_US
dc.titlePrevalent expression of the immunostimulatory MHC class I chain–related molecule is counteracted by shedding in prostate canceren_US


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