Augmented serum level of major histocompatibility complex class I-related chain A (MICA) protein and reduced NKG2D expression on NK and T cells in patients with cervical cancer and precursor lesions.

Augmented serum level of major histocompatibility complex class I-related chain A (MICA) protein and reduced NKG2D expression on NK and T cells in patients with cervical cancer and precursor lesions.
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DOI:
10.1186/1471-2407-8-16
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发表时间:
2008-01-21
期刊:
影响因子:
3.8
通讯作者:
Del Toro-Arreola S
Del Toro-Arreola S
中科院分区:
医学2区
文献类型:
--
作者:
Arreygue-Garcia NA;Daneri-Navarro A;del Toro-Arreola A;Cid-Arregui A;Gonzalez-Ramella O;Jave-Suarez LF;Aguilar-Lemarroy A;Troyo-Sanroman R;Bravo-Cuellar A;Delgado-Rizo V;Garcia-Iglesias T;Hernandez-Flores G;Del Toro-Arreola S

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子宫颈癌是全世界妇女中第二大常见癌症。NK细胞和细胞毒性T细胞通过NKG2D激活受体在消灭病毒感染细胞和肿瘤细胞中发挥重要作用,NKG2D激活受体通过结合主要组织相容性复合体i类相关链A (MICA)蛋白促进靶细胞裂解。在上皮性肿瘤患者中发现血清MICA水平升高。本研究的目的是比较来自宫颈癌患者或前驱病变患者的血液样本中表达可溶性MICA (sMICA)和nkg2d的NK和T细胞的水平。收集含肝素或不含肝素的外周血,分别获得单个核细胞或血清。ELISA法检测血清sMICA水平,流式细胞术检测表达nkg2d的免疫细胞。此外,还进行了sMICA水平与NKG2D表达或病变分期的相关性分析。几乎所有患者的血清中都检测到大量的sMICA。我们发现,与健康供者相比,宫颈癌和病变组中表达nkg2d的NK和T细胞的数量都有所减少。Pearson分析显示sMICA与表达nkg2d的T细胞呈负相关;然而,当我们将分析应用于NK细胞上sMICA和NKG2D的表达时,我们没有发现显著的相关性。我们的研究结果首次表明,与健康供者相比,在宫颈癌患者和前驱病变患者的血清中都发现了高水平的sMICA。我们还观察到患者样本中表达nkg2d的NK和T细胞数量减少;然而,sMICA和NKG2D表达之间的负相关仅在T细胞中可见。
Cervical cancer is the second most common cancer in women worldwide. NK and cytotoxic T cells play an important role in the elimination of virus-infected and tumor cells through NKG2D activating receptors, which can promote the lysis of target cells by binding to the major histocompatibility complex class I-related chain A (MICA) proteins. Increased serum levels of MICA have been found in patients with epithelial tumors. The aim of this study was to compare the levels of soluble MICA (sMICA) and NKG2D-expressing NK and T cells in blood samples from patients with cervical cancer or precursor lesions with those from healthy donors. Peripheral blood with or without heparin was collected to obtain mononuclear cells or sera, respectively. Serum sMICA levels were measured by ELISA and NKG2D-expressing immune cells were analyzed by flow cytometry. Also, a correlation analysis was performed to associate sMICA levels with either NKG2D expression or with the stage of the lesion. Significant amounts of sMICA were detected in sera from nearly all patients. We found a decrease in the number of NKG2D-expressing NK and T cells in both cervical cancer and lesion groups when compared to healthy donors. Pearson analysis showed a negative correlation between sMICA and NKG2D-expressing T cells; however, we did not find a significant correlation when the analysis was applied to sMICA and NKG2D expression on NK cells. Our results show for the first time that high sMICA levels are found in sera from patients with both cervical cancer and precursor lesions when compared with healthy donors. We also observed a diminution in the number of NKG2D-expressing NK and T cells in the patient samples; however, a significant negative correlation between sMICA and NKG2D expression was only seen in T cells.
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