Identification of 41g-B7-H3 as a neuroblastoma-associated molecule that exerts a protective role from an NK cell-mediated lysis
Identification of 41g-B7-H3 as a neuroblastoma-associated molecule that exerts a protective role from an NK cell-mediated lysis
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DOI：
10.1073/pnas.0405025101
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发表时间：
2004-08-24
影响因子：
11.1
通讯作者：
Bottino, C
中科院分区：
文献类型：
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作者：
Castriconi, R;Dondero, A;Bottino, C
在这项研究中，为了鉴定神经母细胞瘤相关的表面抗原，我们制备了针对ACN神经母细胞瘤细胞系的单克隆抗体。我们选择了一种mAb (5B14)，它与所有分析的神经母细胞瘤细胞系反应，并允许检测神经母细胞瘤患者骨髓抽吸液中的肿瘤细胞浸润。在细胞荧光分析中，与抗双胞苷单抗不同，5B14单抗与正常骨髓造血细胞前体没有反应性，因此代表了识别神经母细胞瘤细胞的高度特异性标记。分子分析显示5B14单抗活性表面糖蛋白与最近鉴定的41g-B7-H3分子相对应。值得注意的是，单抗介导的41g-B7-H3分子在细胞转染物或新分离的神经母细胞瘤细胞上的掩膜可增强自然杀伤细胞介导的靶细胞裂解。这些数据表明，在肿瘤细胞表面表达的41g-B7-H3分子可以通过与自然杀伤细胞上表达的一种尚未确定的抑制受体相互作用，对自然杀伤细胞介导的裂解发挥保护作用。
In this study, in an attempt to identify neuroblastoma-associated surface antigens, we generated mAbs against the ACN neuroblastoma cell line. A mAb was selected (5B14) that reacted with all neuroblastoma cell lines analyzed and allowed detection of tumor cell infiltrates in bone marrow aspirates from neuroblastoma patients. In cytofluorimetric analysis, unlike anti-disialoganglioside mAb, 5B14 mAb did not display reactivity with normal bone marrow hematopoietic cell precursors, thus representing a highly specific marker for identifying neuroblastoma cells. Molecular analysis revealed that the 5B14 mAb-reactive surface glycoprotein corresponded to the recently identified 41g-B7-H3 molecule. Remarkably, mAb-mediated masking of the 41g-B7-H3 molecule on cell transfectants or on freshly isolated neuroblastoma cells resulted in enhancement of natural killer-mediated lysis of these target cells. These data suggest that 41g-B7-H3 molecules expressed at the tumor cell surface can exert a protective role from natural killer-mediated lysis by interacting with a still undefined inhibitory receptor expressed on natural killer cells.