Prevalent expression of the immunostimulatory MHC class I chain–related molecule is counteracted by shedding in prostate cancer

ResearchWorks/Manakin Repository

Search ResearchWorks


Advanced Search

Browse

My Account

Statistics

Related Information

Prevalent expression of the immunostimulatory MHC class I chain–related molecule is counteracted by shedding in prostate cancer

Show full item record

Title: Prevalent expression of the immunostimulatory MHC class I chain–related molecule is counteracted by shedding in prostate cancer
Author: Wu, Jennifer D.; Higgins, Lily M.; Steinle, Alexander; Cosman, David; Haugk, Kathy; Plymate, Stephen R.
Abstract: The 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.
URI: http://www.jci.org/articles/view/22206
http://hdl.handle.net/1773/15883

Files in this item

Files Size Format View
Wu1.pdf 744.5Kb PDF View/Open

This item appears in the following Collection(s)

Show full item record