Siglec-7 is an indicator of natural killer cell function in acute myeloid leukemia
Siglec-7 is an indicator of natural killer cell function in acute myeloid leukemia
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Siglec-7 是急性髓系白血病自然杀伤细胞功能的指标
DOI：
10.1016/j.intimp.2021.107965
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发表时间：
2021
影响因子：
5.6
通讯作者：
Wang Xuefu
中科院分区：
文献类型：
--
作者：
Yang Liu;Feng Yuanyuan;Wang Shanshan;Jiang Shanyue;Tao Longxiang;Li Jing;Wang Xuefu
免疫功能障碍是急性髓细胞白血病（AML）的一个既定危险因素。自然杀伤（NK）细胞的细胞毒性在AML中大大受损，NK细胞受体谱在AML中显著改变;然而，这尚未得到很好的表征。在这项研究中，我们发现Siglec-7的下调可以用作AML中NK细胞功能障碍的潜在标志物。与健康对照组相比，AML患者外周血中NK细胞的绝对数量和百分比下降，AML患者NK细胞中活化受体NKG 2D、NKp 46和NKp 30的水平降低。相反，AML患者的NK细胞中抑制性受体TIM-3、ILT-4、ILT-5和PD-1的水平升高。值得注意的是，来自AML患者的NK细胞中Siglec-7的水平显著低于来自健康对照的NK细胞中的水平，并且当与Siglec-7-NK细胞相比时，Siglec-7+NK细胞显示出更高水平的活化受体和更强的细胞毒性。我们的数据表明，降低的Siglec-7水平可以预测AML中的NK细胞功能障碍，NK细胞可能是AML免疫治疗的有希望的靶点。
Immune dysfunction is an established risk factor in acute myeloid leukemia (AML). The cytotoxicity of natural killer (NK) cells is greatly impaired in AML, and the profile of NK cell receptors is markedly altered in AML; however, this is not yet well characterized. In this study, we found the downregulation of Siglec-7 could be utilized as a potential marker of NK cell dysfunction in AML. The absolute numbers and percentages of NK cells were declined in the peripheral blood of patients with AML, and the levels of activating receptors NKG2D, NKp46, and NKp30 were reduced in NK cells from patients with AML compared with healthy controls. In contrast, the levels of inhibitory receptors TIM-3, ILT-4, ILT-5, and PD-1 were increased in NK cells from patients with AML. Of note, the level of Siglec-7 in NK cells from patients with AML was significantly lower than that in NK cells from healthy controls, and Siglec-7+NK cells displayed higher levels of activating receptors and stronger cytotoxicity when compared with Siglec-7–NK cells. Our data indicate that decreased Siglec-7 level may predict NK cell dysfunction in AML, and NK cells may be promising targets of immunotherapy for AML.