Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.
Oncol Res Treat. 2019;42(4):202-208. doi: 10.1159/000497208. Epub 2019 Mar 14.
In this study, the expression pattern of NKp30 and T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3), as candidates for activating and inhibitory receptors of NK cells, were evaluated in patients with chronic lymphocytic leukemia (CLL).
24 CLL patients and 19 healthy controls were enrolled. Fresh peripheral blood was collected from all subjects and stained with fluorochrome-conjugated antibodies. The frequency of CD56+/CD3-/NKp30+ and CD56+/CD3-/Tim-3+ cells was determined by multicolor flow cytometry.
Our results revealed that Tim-3 is significantly upregulated on natural killer (NK) cells of CLL patients in comparison to healthy controls. NK cells of CLL patients showed lower expression of NKp30-activating receptor compared to controls. Tim-3 expression pattern on NK cells of CLL patients was correlated with poor prognostic factors including low hemoglobin level, high absolute lymphocyte count, and high serum C-reactive protein level.
Dysregulated expression of Tim-3 and NKp30 receptors confirms the exhaustion state of NK cells in CLL. Our data introduce Tim-3 as a promising biomarker and potential target for immunotherapy of CLL.
在这项研究中，我们评估了 NKp30 和 T 细胞免疫球蛋白和粘蛋白结构域蛋白 3（Tim-3）作为 NK 细胞激活和抑制受体候选物在慢性淋巴细胞白血病（CLL）患者中的表达模式。
共纳入 24 例 CLL 患者和 19 例健康对照者。所有研究对象均采集新鲜外周血，并用荧光素标记的抗体进行染色。采用多色流式细胞术检测 CD56+/CD3-/NKp30+和 CD56+/CD3-/Tim-3+细胞的频率。
与健康对照组相比，CLL 患者 NK 细胞上的 Tim-3 显著上调。与对照组相比，CLL 患者 NK 细胞上 NKp30 激活受体的表达较低。CLL 患者 NK 细胞上 Tim-3 的表达模式与不良预后因素相关，包括低血红蛋白水平、高绝对淋巴细胞计数和高血清 C 反应蛋白水平。
Tim-3 和 NKp30 受体的失调表达证实了 CLL 中 NK 细胞的耗竭状态。我们的数据表明 Tim-3 是 CLL 免疫治疗有前途的生物标志物和潜在靶点。
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