School of Pharmacy, Anhui Medical University, Hefei 230032, China.
Department of Hematology, Anhui Provincial Cancer Hospital, Hefei 230031, China.
Int Immunopharmacol. 2021 Oct;99:107965. doi: 10.1016/j.intimp.2021.107965. Epub 2021 Jul 14.
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.
免疫功能障碍是急性髓系白血病（AML）的既定风险因素。自然杀伤（NK）细胞的细胞毒性在 AML 中受到严重损害，NK 细胞受体的谱在 AML 中明显改变；然而，这尚未得到很好的描述。在这项研究中，我们发现 Siglec-7 的下调可作为 AML 中 NK 细胞功能障碍的潜在标志物。AML 患者外周血中的 NK 细胞绝对数和百分比下降，与健康对照组相比，AML 患者 NK 细胞中激活受体 NKG2D、NKp46 和 NKp30 的水平降低。相比之下，AML 患者 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，AML 患者 NK 细胞中的 Siglec-7 水平明显低于健康对照组 NK 细胞中的 Siglec-7 水平，与 Siglec-7 NK 细胞相比，Siglec-7 NK 细胞具有更高水平的激活受体和更强的细胞毒性。我们的数据表明，Siglec-7 水平降低可能预示着 AML 中 NK 细胞功能障碍，NK 细胞可能是 AML 免疫治疗的有前途的靶点。
