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外周血 Th17、Th1、IL-17 和 IFN-γ 水平与有无肝硬化的不可切除肝细胞癌患者 TACE 反应的相关性。

The Association between Peripheral Th17, Th1, IL-17, and IFN-γ Levels and TACE Response in Patients with Unresectable Hepatocellular Carcinoma with or without Cirrhosis.

机构信息

Division of Hepatobiliary, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia - Cipto Mangunkusumo Hospital, Jakarta.

出版信息

Acta Med Indones. 2020 Oct;52(4):326-333.

Abstract

BACKGROUND

Th17 cells, a subset of CD4+ T cells with the capacity to produce IL-17, were reported to have pro-tumor and anti-tumor effects. Th1 cells are known for their capacity to eliminate tumor cells by producing IFN-γ. Transarterial chemoembolization (TACE) is a treatment of choice for patients with unresectable hepatocellular carcinoma (HCC). Therefore, this study aimed to determine the association between peripheral Th17, Th1, IL-17, and IFN-γ levels and TACE response in patients with unresectable HCC with or without cirrhosis.

METHODS

a prospective cohort study was conducted in Cipto Mangunkusumo Hospital and several affiliated hospitals from June 2015 to January 2019. HCC patients with or without cirrhosis who met the inclusion criteria were included in this study. Blood samples were obtained immediately before TACE and 30 days after TACE. Th1 and Th17 cells were analyzed by flowcytometry, while IL-17 and IFN-γ were examined with ELISA method. TACE response was assessed with mRECIST.

RESULTS

forty-one HCC patients were enrolled in this study. According to mRECIST, 12 patients were assessed as response group (complete and partial response) and 29 patients were assessed as nonresponse group (stable and progressive disease). Levels of Th1 and Th17 increased significantly after TACE in the response group. On the other hand, IL-17 and IFN-γ decreased after TACE in both groups, although not statistically significant. Interestingly, in the response group, a significant increase was found in the number of T cells subset showing both IFN-γ and IL-17 markers on their surfaces, i.e. CD4+/IFN-γ+/IL-17+ T cells.

CONCLUSION

increased circulating Th1, Th17, and CD4+/IFN-γ+/IL-17+ T cells were observed in HCC patients with complete or partial response to TACE.

摘要

背景

Th17 细胞是具有产生 IL-17 能力的 CD4+T 细胞亚群,据报道具有促肿瘤和抗肿瘤作用。Th1 细胞通过产生 IFN-γ 而具有消除肿瘤细胞的能力。经动脉化疗栓塞(TACE)是不可切除肝细胞癌(HCC)患者的首选治疗方法。因此,本研究旨在确定外周 Th17、Th1、IL-17 和 IFN-γ 水平与有无肝硬化的不可切除 HCC 患者 TACE 反应之间的关系。

方法

这是一项于 2015 年 6 月至 2019 年 1 月在 Cipto Mangunkusumo 医院和几家附属医院进行的前瞻性队列研究。符合纳入标准的 HCC 患者无论有无肝硬化均纳入本研究。在 TACE 前和 TACE 后 30 天采集血液样本。通过流式细胞术分析 Th1 和 Th17 细胞,通过 ELISA 法检测 IL-17 和 IFN-γ。用 mRECIST 评估 TACE 反应。

结果

本研究纳入了 41 例 HCC 患者。根据 mRECIST,12 例患者被评估为反应组(完全和部分缓解),29 例患者被评估为非反应组(稳定和进展性疾病)。在反应组中,TACE 后 Th1 和 Th17 水平显著升高。另一方面,两组 IL-17 和 IFN-γ 均下降,但无统计学意义。有趣的是,在反应组中,CD4+/IFN-γ+/IL-17+T 细胞表面同时显示 IFN-γ 和 IL-17 标志物的 T 细胞亚群数量显著增加。

结论

在 TACE 完全或部分缓解的 HCC 患者中观察到循环 Th1、Th17 和 CD4+/IFN-γ+/IL-17+T 细胞增加。

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