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宫颈癌患者外周血中淋巴细胞程序性死亡蛋白-1及单核细胞程序性死亡配体-1的表达及临床意义

Expression and clinical significance of programmed death-1 on lymphocytes and programmed death ligand-1 on monocytes in the peripheral blood of patients with cervical cancer.

作者信息

Zhang Ying, Zhu Weipei, Zhang Xueguang, Qu Qiuxia, Zhang Liyuan

机构信息

Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.

Research Institute of Immunology, Soochow University, Suzhou, Jiangsu 215000, P.R. China.

出版信息

Oncol Lett. 2017 Dec;14(6):7225-7231. doi: 10.3892/ol.2017.7105. Epub 2017 Sep 29.

Abstract

The programmed death-1 (PD-1) signaling pathway serves a critical role in immune regulation and tolerance by suppressing the activation and proliferation of T cells. The aim of the present study was to investigate the effect of PD-1 and programmed death-ligand 1 (PD-L1) on the development of cervical carcinoma and cervical intraepithelial neoplasia (CIN). A total of 40 healthy controls (HC), 40 patients with CIN and 66 newly diagnosed cervical cancer patients were recruited. The expression level of PD-1 expression on peripheral cluster of differentiation (CD)4 and CD8 T cells and PD-L1 on monocytes was analyzed by flow cytometry. The expression level of soluble PD-L1 in serum was determined by an ELISA. The results of the present study demonstrated that the PD-1 expression level on CD4 and CD8 T cells was significantly increased in CIN and cervical cancer, compared with that in HC. In addition, the PD-1 expression level on CD4 and CD8 T cells was increased in cervical cancer, compared with that in CIN. However, the expression level of PDL-1 on CD14 monocytes was increased in cancer and CIN, but limited in cancer and CIN. In addition, PD-1 expression on CD4 T cells was positively associated with PD-1 expression on CD8 T cells in cervical cancer (P<0.05). Further analyses revealed that the proportion of PD-1 on CD4 and CD8 T cells were positively associated with tumor stages. However, no difference in the degree of soluble PD-1 among cancer, CIN and HC cells was revealed. The results suggested that the PD-1 signaling pathway is involved in the development of CIN and cervical cancer.

摘要

程序性死亡蛋白-1(PD-1)信号通路通过抑制T细胞的激活和增殖在免疫调节和耐受中发挥关键作用。本研究旨在探讨PD-1和程序性死亡配体1(PD-L1)对宫颈癌和宫颈上皮内瘤变(CIN)发生发展的影响。共招募了40名健康对照者(HC)、40名CIN患者和66名新诊断的宫颈癌患者。采用流式细胞术分析外周分化簇(CD)4和CD8 T细胞上PD-1的表达水平以及单核细胞上PD-L1的表达水平。采用酶联免疫吸附测定法(ELISA)测定血清中可溶性PD-L1的表达水平。本研究结果表明,与HC相比,CIN和宫颈癌患者CD4和CD8 T细胞上的PD-1表达水平显著升高。此外,与CIN相比,宫颈癌患者CD4和CD8 T细胞上的PD-1表达水平升高。然而,CD14单核细胞上PDL-1的表达水平在癌症和CIN中升高,但在癌症和CIN中有限。此外,宫颈癌患者CD4 T细胞上的PD-1表达与CD8 T细胞上的PD-1表达呈正相关(P<0.05)。进一步分析显示,CD4和CD8 T细胞上PD-1的比例与肿瘤分期呈正相关。然而,癌症、CIN和HC细胞中可溶性PD-1的程度没有差异。结果表明,PD-1信号通路参与了CIN和宫颈癌的发生发展过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/89d4/5754902/2c397bdd0679/ol-14-06-7225-g00.jpg

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