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Th17细胞与白细胞介素-17作为卵巢癌治疗中的新型免疫靶点

Th17 Cells and IL-17 As Novel Immune Targets in Ovarian Cancer Therapy.

作者信息

Bilska Monika, Pawłowska Anna, Zakrzewska Ewelina, Chudzik Agata, Suszczyk Dorota, Gogacz Marek, Wertel Iwona

机构信息

The First Department of Oncological Gynecology and Gynecology in Independent Public Teaching Hospital No. 1 in Lublin (Poland), Staszica 16, 20-081 Lublin, Poland.

Independent Laboratory of Cancer Diagnostics and Immunology, The First Department of Gynecologic Oncology and Gynaecology, Medical University of Lublin, Staszica 16, Lublin 20-081, Poland.

出版信息

J Oncol. 2020 Feb 21;2020:8797683. doi: 10.1155/2020/8797683. eCollection 2020.

DOI:10.1155/2020/8797683
PMID:32148497
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7054820/
Abstract

Ovarian cancer (OC) is usually diagnosed at an advanced stage and is related with poor prognosis. Despite numerous studies, the pathogenesis of OC is still unknown. Recent studies indicate the role of the immune system in the development and spread of OC. The identification of factors and mechanisms involved in that process and their modulation is crucial for creating effective antitumor therapy. We investigated the potential role of Th17 cells in OC patients ( = 71) by analyzing the frequencies of Th17 cells in three different environments, i.e., peripheral blood (PB), peritoneal fluid (PF), and tissue (Th17 infiltrating cells), and the concentration of IL-17A in plasma and PF of patients in terms of their clinical and prognostic significance. Th17 cells were analyzed by flow cytometry as a percentage of CD4 lymphocytes that expressed intracellular expression of IL-17A. The level of IL-17A in plasma and PF were determined by ELISA. Our results showed accumulation of Th17 cells among tumor-infiltrating CD4 lymphocytes ( < 0.001 in relation to PB). Moreover, the percentage of Th17 cells in both PB and PF of OC patients was significantly lower than that in benign tumors group ( = 35). There were no significant differences in the percentage of Th17 cells in PB, PF, and tissue in relation to clinicopathological characteristics of OC patients and survival. The lower percentage of Th17 cells in the PB and PF of OC patients may promote evasion of host immune response by cancer cells. The concentration of IL-17A in plasma of OC patients was higher ( < 0.0001) than that in both benign tumors and control group ( = 10). The PF IL-17A level in OC patients was higher ( < 0.0001) than that in women with benign ovarian tumors, indicating its synthesis in OC microenvironment. Higher IL-17A level in PF is correlated with longer (median: 36.5 vs. 27 months) survival of OC patients.

摘要

卵巢癌(OC)通常在晚期被诊断出来,且预后较差。尽管进行了大量研究,但OC的发病机制仍然未知。最近的研究表明免疫系统在OC的发生和扩散中起作用。识别参与该过程的因素和机制及其调节对于创建有效的抗肿瘤治疗至关重要。我们通过分析三种不同环境(即外周血(PB)、腹腔积液(PF)和组织(Th17浸润细胞))中Th17细胞的频率,以及患者血浆和PF中IL-17A的浓度,研究了Th17细胞在OC患者(n = 71)中的潜在作用,涉及它们的临床和预后意义。通过流式细胞术分析Th17细胞,将其作为表达细胞内IL-17A的CD4淋巴细胞的百分比。通过酶联免疫吸附测定法(ELISA)测定血浆和PF中IL-17A的水平。我们的结果显示肿瘤浸润的CD4淋巴细胞中Th17细胞积聚(与PB相比,P < 0.001)。此外,OC患者PB和PF中Th17细胞百分比显著低于良性肿瘤组(n = 35)。PB、PF和组织中Th17细胞百分比与OC患者的临床病理特征及生存率无显著差异。OC患者PB和PF中Th17细胞百分比降低可能促进癌细胞逃避宿主免疫反应。OC患者血浆中IL-17A浓度高于良性肿瘤组和对照组(n = 10)(P < 0.0001)。OC患者PF中IL-17A水平高于卵巢良性肿瘤女性(P < 0.0001),表明其在OC微环境中合成。PF中较高的IL-17A水平与OC患者较长的(中位数:36.5个月对27个月)生存期相关。

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