title: Soluble MICB in malignant diseases: analysis of diagnostic significance and correlation with soluble MICA.
abstract: Expression of ligands of the immunoreceptor NKG2D such as MICA and MICB has been proposed to play an important role in the immunosurveillance of tumors. Proteolytic shedding of NKG2D ligands from cancer cells therefore constitutes an immune escape mechanism impairing anti-tumor reactivity by NKG2D-bearing cytotoxic lymphocytes. Serum levels of sMICA have been shown to be of diagnostic significance in malignant diseases of various origins. Here, we investigated the potential of soluble MICB, the sister molecule of MICA, as a marker in cancer and its correlation with soluble MICA. Analysis of MICB in sera of 512 individuals revealed slightly higher MICB levels in patients with various malignancies (N = 296; 95th percentile 216 pg/ml; P = 0.069) than in healthy individuals (N = 62; 95th percentile 51 pg/ml). Patients with benign diseases (N = 154; 95th percentile 198 pg/ml) exhibited intermediate MICB levels. In cancer patients, elevated MICB levels correlated significantly with cancer stage and metastasis (P = 0.007 and 0.007, respectively). Between MICB and MICA levels, only a weak correlation was found (r = 0.24). Combination of both markers resulted only in a slightly higher diagnostic power in the high specificity range. The reduction of MICA and MICB surface expression on cells by shedding and the effects of sMICA and sMICB in serum on host lymphocyte NKG2D expression might play a role in late stages of tumor progression by overcoming the confining effect of NK cells and CD8 T cells. While MICB levels are not suited for the diagnosis of cancer in early stages, they may provide additional information for the staging of cancer disease.
authors.affiliation: Institute of Clinical Chemistry, University Hospital of Munich, Ludwig-Maximilians-University, Marchioninistr. 15, Munich, 81377, Germany Stefan.Holdenrieder@med.uni-muenchen.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Holdenrieder
authors.forename: Petra
authors.initials: P
authors.lastname: Stieber
authors.forename: Andrea
authors.initials: A
authors.lastname: Peterfi
authors.forename: Dorothea
authors.initials: D
authors.lastname: Nagel
authors.forename: Alexander
authors.initials: A
authors.lastname: Steinle
authors.forename: Helmut Rainer
authors.initials: HR
authors.lastname: Salih
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D015395:Histocompatibility Antigens Class I / Q000097:blood* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009367:Neoplasm Staging; D009369:Neoplasms / Q000175:diagnosis*; D011971:Receptors, Immunologic / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D012995:Solubility
chemical_list: D014408:Biomarkers, Tumor; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; D008024:Ligands; C099187:MHC class I-related chain A; C098080:MICB antigen; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell