Holdenrieder Stefan, Stieber Petra, Peterfi Andrea, Nagel Dorothea, Steinle Alexander, Salih Helmut Rainer
Institute of Clinical Chemistry, University Hospital of Munich, Ludwig-Maximilians-University, Marchioninistr. 15, Munich, 81377, Germany
Cancer Immunol Immunother. 2006 Dec;55(12):1584-9. doi: 10.1007/s00262-006-0167-1. Epub 2006 Apr 25.
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.
免疫受体NKG2D的配体如MICA和MICB的表达被认为在肿瘤免疫监视中起重要作用。因此，癌细胞中NKG2D配体的蛋白水解脱落构成了一种免疫逃逸机制，损害了携带NKG2D的细胞毒性淋巴细胞的抗肿瘤反应性。血清sMICA水平已被证明在各种起源的恶性疾病中具有诊断意义。在此，我们研究了可溶性MICB（MICA的姊妹分子）作为癌症标志物的潜力及其与可溶性MICA的相关性。对512名个体血清中的MICB分析显示，各种恶性肿瘤患者（N = 296；第95百分位数为216 pg/ml；P = 0.069）的MICB水平略高于健康个体（N = 62；第95百分位数为51 pg/ml）。良性疾病患者（N = 154；第95百分位数为198 pg/ml）的MICB水平处于中间值。在癌症患者中，升高的MICB水平与癌症分期和转移显著相关（分别为P = 0.007和0.007）。在MICB和MICA水平之间，仅发现微弱的相关性（r = 0.24）。两种标志物的联合仅在高特异性范围内导致略高的诊断能力。通过脱落导致细胞表面MICA和MICB表达的减少以及血清中sMICA和sMICB对宿主淋巴细胞NKG2D表达的影响，可能通过克服NK细胞和CD8 T细胞的限制作用在肿瘤进展的晚期发挥作用。虽然MICB水平不适合早期癌症的诊断，但它们可能为癌症疾病的分期提供额外信息。
