免疫球蛋白 GM 和 FcγRIIIa 基因型影响神经母细胞瘤细胞的细胞毒性。
Immunoglobulin GM and FcγRIIIa genotypes influence cytotoxicity of neuroblastoma cells.
机构信息
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
出版信息
J Neuroimmunol. 2014 May 15;270(1-2):95-7. doi: 10.1016/j.jneuroim.2014.03.003. Epub 2014 Mar 11.
Immunoglobulin GM (γ marker) allotypes are strongly associated with neuroblastoma, but the mechanism is not known. One mechanism could involve antibody-dependent cell-mediated cytotoxicity (ADCC) of neuroblastoma cells. Using an ADCC inhibition assay, we show that IgG1 expressing GM 3+,1-,2- allotypes blocked all phenylalanine-expressing FcγRIIIa present on NK cells, resulting in total inhibition of anti-GD2 antibody-mediated ADCC of GD2-overexpressing neuroblastoma cells. In contrast, the inhibitory effect of this protein was significantly lower when the NK cells were homozygous for the valine allele of FcγRIIIa (100 vs. 21%; p=0.00004). These and other findings presented here could lead to a more effective immunotherapy of neuroblastoma.
免疫球蛋白 GM（γ 标记）同种型与神经母细胞瘤强烈相关，但机制尚不清楚。一种机制可能涉及神经母细胞瘤细胞的抗体依赖性细胞介导的细胞毒性（ADCC）。使用 ADCC 抑制测定法，我们表明表达 GM 3+、1-、2-同种型的 IgG1 阻断了 NK 细胞上所有表达苯丙氨酸的 FcγRIIIa，导致 GD2 过表达神经母细胞瘤细胞对抗 GD2 抗体介导的 ADCC 的完全抑制。相比之下，当 NK 细胞纯合 FcγRIIIa 的缬氨酸等位基因时，这种蛋白质的抑制作用明显降低（100 对 21%；p=0.00004）。这里提出的这些和其他发现可能导致神经母细胞瘤更有效的免疫疗法。
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