Salih Helmut Rainer, Goehlsdorf Dennis, Steinle Alexander
Department of Internal Medicine II, Eberhard-Karls-University Tübingen, 72076 Tübingen, Germany.
Hum Immunol. 2006 Mar;67(3):188-95. doi: 10.1016/j.humimm.2006.02.008. Epub 2006 Mar 29.
MICA, a ligand of the activating immunoreceptor NKG2D, is released by tumor cells in a soluble form and can be detected in sera of tumor patients at significant levels. Soluble MICA has been proposed to counteract NKG2D-mediated immunosurveillance of tumors. Here, we report that MICB, the second member of the human MIC protein family, is likewise shed by metalloproteases from tumor cells and is present in sera of patients with gastrointestinal tumors. While cell-bound MICB causes downregulation of surface NKG2D, soluble MICB did not alter NKG2D expression on NK cells in vitro. Thus, proteolytic shedding of MICB by tumor cells may impair immunogenicity of tumors primarily by reducing NKG2D-ligand densities on malignant cells.
MICA是激活免疫受体NKG2D的配体，由肿瘤细胞以可溶性形式释放，并且在肿瘤患者血清中能够被检测到显著水平。可溶性MICA被认为可抵消NKG2D介导的肿瘤免疫监视。在此，我们报告称，人类MIC蛋白家族的第二个成员MICB同样会被肿瘤细胞中的金属蛋白酶切割释放，并存在于胃肠道肿瘤患者的血清中。虽然细胞结合型MICB会导致表面NKG2D下调，但可溶性MICB在体外并未改变NK细胞上NKG2D的表达。因此，肿瘤细胞对MICB的蛋白水解切割可能主要通过降低恶性细胞上NKG2D配体密度来损害肿瘤的免疫原性。
