NEW YORK (Reuters Health) - Serum levels of soluble MHC class I chain-related molecules (sMIC) are increased in patients with advanced prostate cancer and “may be a novel biomarker,” according to a report in the August 16th issue of The Journal of Clinical Investigation.
When MIC engages the NKG2D receptor on natural killer cells, the cells are activated and boost the anti-tumor immune response, the authors explain. Paradoxically, however, malignant tumors of various kinds shed MIC and may subsequently “evade MIC-NKG2D-mediated immunity.”
How shedding or impairment of MIC in NKG2D-mediated immune function correlates with disease stages or progression is unknown.
Dr. Jennifer D. Wu from the University of Washington in Seattle, and colleagues, investigated MIC expression in primary prostate carcinoma and NKG2D-mediated NK cell function in prostate cancer patients at various stages of the disease.
MIC expressed in prostate cancer cell lines elicited NKG2D-dependent activation of NK cells against prostate cancer cells, the authors report. Further observations indicated that MIC is induced in the early stage of prostate cell transformation and is expressed widely in prostate carcinoma but not in normal prostate tissue.
Patients with advanced prostate cancer had significantly higher serum levels of sMIC and significantly impaired NKG2D-mediated NK cell function, the researchers note, but sMIC did not correlate significantly with PSA levels.
Serum sMIC from prostate cancer patients down-modulated the expression of NKG2D on normal NK cells, the investigators report, and restoration of NKG2D-mediated NK cell function by in vitro cytokine stimulation enhanced their cytotoxicity against prostate cancer cells.
“Our study has suggested that a deficiency in MIC-NKG2D immune surveillance may contribute to prostate cancer progression,” the authors conclude. “Our study also suggests that sMIC may potentially be an additional marker for prostate cancer.”
The investigators add, “Our results using cytokines to enhance NKG2D-mediated NK cell function in vitro have provided an alternative for cell-based immune therapy for prostate cancer.”
Source: J Clin Invest 2004;114:560-568. [ Google search on this article ]
MeSH Headings:Biological Factors: Genes, MHC Class I: Genital Neoplasms, Male: Immunologic and Biological Factors: Neoplasms: Neoplasms by Site: Prostatic Neoplasms: Urogenital Neoplasms: Histocompatibility Antigens Class I: Biological Markers: Chemical Actions and Uses: Chemical Actions: Chemicals and Drugs: DiseasesCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
