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免疫谱的变化影响肝癌的疾病进展。

Changes in immune profile affect disease progression in hepatocellular carcinoma.

机构信息

Department of Immunology, School of Medicine, 48455Isfahan University of Medical Sciences, Isfahan, Iran.

Division of Transplant Services, Department of Surgery, 12302SUNY Upstate Medical University Syracuse, Syracuse, NY, USA.

出版信息

Int J Immunopathol Pharmacol. 2022 Jan-Dec;36:3946320221078476. doi: 10.1177/03946320221078476.

Abstract

Hepatocellular carcinoma (HCC) as a chronic liver condition is largely associated with immune responses. Previous studies have revealed that different subsets of lymphocytes play fundamental roles in controlling or improving the development and outcome of solid tumors like HCC. Hence, this study aimed to investigate whether immune system changes were related to disease development in HCC patients. Peripheral blood mononuclear cells were isolated from 30 HCC patients and 30 healthy volunteers using Ficoll density centrifugation. The isolated cells were stained with different primary antibodies and percentages of different immune cells were determined by flow cytometry. HCC patients indicated significant reductions in the numbers of CD4 cells, Tbet+IFNγ+cells, and GATA+IL-4+cells in peripheral blood in comparison with healthy individuals ( < 0.05). There was no significant change in IL-17+RORγt+cells between patient and healthy groups. In contrast, Foxp3+CD127cell frequency was significantly higher in patients than healthy subjects ( < 0.0001). The numbers of Th1, Th2, and Th17 cells were significantly lower in HCC patients than healthy control ( < 0.0001), although the reduction in Th2 cell numbers was not statistically significant. On the contrary, Treg percentage showed a significant increase in patients compared to healthy subjects ( < 0.0001). Other data revealed that Th1, Th2, and Th17 cell frequencies were significantly higher in healthy individuals than patients with different TNM stages of HCC, with the exception of Th2 in patients with stage II HCC ( < 0.01-0.05). Treg percentage was significantly increased in patients with different TNM stages ( < 0.0001). Among all CD4 T cells, the frequency of Th2 cell was significantly associated with TNM stages of HCC ( < 0.05). Our data provide further evidence to show that immune changes may participate in determining HCC progression and disease outcome. However, it should be mentioned that more investigations are needed to clarify our results and explain possible impacts of other immune cells on the pathogenesis of HCC.

摘要

肝细胞癌(HCC)作为一种慢性肝脏疾病,与免疫反应密切相关。先前的研究表明,不同的淋巴细胞亚群在控制或改善实体瘤(如 HCC)的发展和结局方面发挥着重要作用。因此,本研究旨在探讨免疫系统变化是否与 HCC 患者的疾病发展有关。

使用 Ficoll 密度离心法从 30 名 HCC 患者和 30 名健康志愿者中分离外周血单核细胞。用不同的初级抗体对分离的细胞进行染色,并通过流式细胞术确定不同免疫细胞的百分比。与健康个体相比,HCC 患者外周血中 CD4 细胞、Tbet+IFNγ+细胞和 GATA+IL-4+细胞的数量明显减少(<0.05)。患者组和健康组之间的 IL-17+RORγt+细胞无显著差异。相反,Foxp3+CD127+细胞在患者中的频率明显高于健康对照组(<0.0001)。与健康对照组相比,HCC 患者 Th1、Th2 和 Th17 细胞的数量明显减少(<0.0001),尽管 Th2 细胞数量的减少无统计学意义。相反,与健康对照组相比,患者组 Treg 百分比显著升高(<0.0001)。其他数据显示,与不同 TNM 分期的 HCC 患者相比,健康个体的 Th1、Th2 和 Th17 细胞频率更高,除了 II 期 HCC 患者的 Th2 细胞(<0.01-0.05)。Treg 百分比在不同 TNM 分期的患者中显著升高(<0.0001)。在所有 CD4 T 细胞中,Th2 细胞的频率与 HCC 的 TNM 分期显著相关(<0.05)。

我们的数据进一步表明,免疫变化可能参与决定 HCC 的进展和疾病结局。然而,应该指出的是,需要更多的研究来澄清我们的结果,并解释其他免疫细胞对 HCC 发病机制的可能影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7757/8891922/f82e1c6fd07d/10.1177_03946320221078476-fig1.jpg

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