Soluble MICA in malignant diseases

Authors

  • Stefan Holdenrieder,

    Corresponding author
    1. Institute of Clinical Chemistry, University Hospital of Munich-Grosshadern, Ludwig-Maximilians-University, Munich, Germany
    • Institute of Clinical Chemistry, University Hospital of Munich, Ludwig Maximilians University, Marchioninistr. 15, 81377 Munich, Germany
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    • Fax: +49-89-7095-6298.

  • Petra Stieber,

    1. Institute of Clinical Chemistry, University Hospital of Munich-Grosshadern, Ludwig-Maximilians-University, Munich, Germany
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  • Andrea Peterfi,

    1. Department of Internal Medicine II, University Hospital of Tuebingen, Eberhard-Karls-University, Tuebingen, Germany
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  • Dorothea Nagel,

    1. Institute of Clinical Chemistry, University Hospital of Munich-Grosshadern, Ludwig-Maximilians-University, Munich, Germany
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  • Alexander Steinle,

    1. Department of Immunology, Institute for Cell Biology, Eberhard-Karls-University, Tuebingen, Germany
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    • The last 2 authors contributed equally to this work.

  • Helmut Rainer Salih

    1. Department of Internal Medicine II, University Hospital of Tuebingen, Eberhard-Karls-University, Tuebingen, Germany
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    • The last 2 authors contributed equally to this work.


Abstract

The immunoreceptor NKG2D activates natural killer cells and costimulates CD8 T cells. The MHC class I–related MICA molecules are ligands of NKG2D and are expressed on malignant, but not on normal, cells. As NKG2D plays an important role in the immunosurveillance of tumors, studies suggest that release of MICA from cancer cells constitutes an immune escape mechanism that systemically impairs antitumor immunity. Here, we investigated the potential of soluble MICA (sMICA) as a marker in cancer. Analysis of sMICA in sera of 512 individuals revealed significantly (p < 0.0001) higher levels in patients with various malignancies (n = 296, median 161 pg/ml) than in healthy individuals (n = 62, median <30 pg/ml). Patients with benign diseases (n = 154, median 84 pg/ml) exhibited intermediate sMICA levels. In cancer patients, elevated sMICA levels correlated significantly with cancer stage and metastasis (p = 0.015 and p = 0.007, respectively). While release of MICA is thought to impair tumor immunity, determination of sMICA levels may provide useful additional information in the diagnosis and staging of cancer. © 2005 Wiley-Liss, Inc.

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