The Stage Dependent Changes in NK Cell Activity and the Expression of Activating and Inhibitory NK Cell Receptors in Melanoma Patients
The Stage Dependent Changes in NK Cell Activity and the Expression of Activating and Inhibitory NK Cell Receptors in Melanoma Patients
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DOI：
10.1016/j.jss.2010.05.012
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发表时间：
2011-12-01
影响因子：
2.2
通讯作者：
Inic, Momcilo
中科院分区：
文献类型：
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作者：
Martinovic, Katarina Mirjacic;Konjevic, Gordana;Inic, Momcilo
背景由于NK细胞的抗肿瘤活性是由许多激活和抑制受体之间的平衡调节，本研究的目的是分析这些受体表达的变化，以及在不同的临床阶段的黑色素瘤患者与NK细胞活性的差异。通过标准（51）Cr放射性测定分析了三个不同临床阶段的43名黑素瘤患者和17名健康对照的NK细胞活性，以及CD 3-CD 56 + NK细胞及其亚群的百分比和绝对数量，以及脱粒标志物CD 107 a、活化NKG 2D和CD 161以及抑制性KIR、CD 158 a、流式细胞术检测CD 3-CD 56 + NK细胞上的CD 158 b受体。采用酶联免疫吸附试验（ELISA）检测IFN-γ和TNF-α的产生。我们发现，与非转移性相反，转移性黑色素瘤患者的NK细胞活性显著受损，CD 107 a表达降低，IFN-γ和TNF-α的产生减少。此外，与健康对照组相比，这些黑色素瘤患者的活化型NKG 2D受体表达显著降低，与NK细胞毒性呈正相关，而CD 3-CD 56 + NK细胞上的抑制型CD 158 b表达显著增加。在这项研究中，我们发现，转移性黑色素瘤患者的NK细胞活性和活化以及抑制性NK细胞受体的表达有显着的变化。这些结果表明，只有在这个病人组中，抑制性NK细胞受体表达的阻断或激活性NK细胞受体表达的增强可能会促进NK细胞介导的细胞溶解。(C)2011 Elsevier Inc. All rights reserved.
Background. As NK cell antitumor activity is regulated by the balance between numerous activating and inhibitory receptors the aim of this study was to analyze the changes in these receptors expression as well as the differences in their association with NK cell activity in melanoma patients in different clinical stages.Materials and Methods. Forty-three melanoma patients in the three different clinical stages and 17 healthy controls were analyzed for NK cell activity by the standard (51)Cr radioactive assay, as well as for the percentage and absolute number of CD3-CD56+ NK cells and their subsets and the expression of degranulation marker CD107a, activating NKG2D and CD161, and inhibitory KIR, CD158a, and CD158b receptors on CD3-CD56+ NK cells by flow cytometry. IFN-gamma and TNF-alpha PBL production were evaluated by enzyme-linked immunosorbent assay (ELISA).Results. We show that contrary to nonmetastatic, metastatic melanoma patients have significantly impaired NK cell activity, lower CD107a expression, as well as decreased production of IFN-gamma and TNF-alpha. Furthermore, these melanoma patients have a significant decrease in the expression of activating NKG2D receptor, which positively correlates with NK cytotoxicity, and a significant increase in the expression of inhibitory CD158b on CD3-CD56+ NK cells compared with healthy controls.Conclusions. In this study, we show that metastatic melanoma patients have significant changes in NK cell activity and the expression of activating as well as inhibitory NK cell receptors. These results indicate that only in this patient group, the blocking of inhibitory or enhancing of activating NK cell receptor expression may promote NK cell-mediated cytolysis. (C) 2011 Elsevier Inc. All rights reserved.