Soluble MICA in malignant diseases.
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.
Holdenrieder
Stefan
S
Institute of Clinical Chemistry, University Hospital of Munich-Grosshadern, Ludwig-Maximilians-University, Munich, Germany. Stefan.Holdenrieder@med.uni-muenchen.de
Stieber
Petra
P
Peterfi
Andrea
A
Nagel
Dorothea
D
Steinle
Alexander
A
Salih
Helmut Rainer
HR
D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D015395:Histocompatibility Antigens Class I / Q000097:blood*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000097:blood*; D011971:Receptors, Immunologic / Q000097:blood*; D055607:Receptors, Natural Killer Cell; D012680:Sensitivity and Specificity
D014408:Biomarkers, Tumor; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell