Guo Cun-Li, Yang Xiu-Hua, Cheng Wen, Xu Yi, Li Jie-Bing, Sun Yi-Xin, Bi Yu-Mei, Zhang Lei, Wang Qiu-Cheng
The Third Affiliated Hospital, Harbin Medical University, Harbin, China E-mail :
Asian Pac J Cancer Prev. 2014;15(6):2613-8. doi: 10.7314/apjcp.2014.15.6.2613.
Dysfunction of the host immune system in cancer patients can be due to a number of factors, including lymphocyte apoptosis. Several studies showed that Foxp3+T cells take part in inducing this process by expressing FasL in tumor patients. However, the relationship between apoptosis, CD8+T cells and Foxp3+T cells in HCC patients is still unclear. The present study was designed to investigate the correlation between apoptosis levels and Fas/FasL expression in CD8+T lymphocytes and Foxp3+T cells in patients with HCC.
CD8+T cells and CD3+Foxp3+T cells were tested from peripheral blood of HCC patients and normal controls and subjected to multicolor flow cytometry. The expression of an apoptosis marker (annexin V) and the death receptor Fas in CD8+T cells and FasL in CD3+Foxp3+T cells were evaluated. Serum TGF-β1 levels in patients with HCC were measured by enzyme-linked immunosorbent assay. The relationship between apoptosis and Fas expression, as well as FasL expression in CD3+Foxp3+T cells was then evaluated.
The frequency of CD8+T cells binding annexin V and Fas expression in CD8+T cells, were all higher in HCC patients than normal controls and the proportion of apoptotic CD8+T cells correlated with their Fas expression. Serum TGF-β1 levels correlated inversely with CD3+Foxp3+T cells.
Fas/FasL interactions might lead to excessive turnover of CD8+T cells and reduce anti-tumor immune responses in patients with HCC. Further investigations of apoptosis induction in Fas+CD8+T cells in vitro are required.
癌症患者体内宿主免疫系统功能失调可能由多种因素导致,包括淋巴细胞凋亡。多项研究表明,在肿瘤患者中,Foxp3⁺T细胞通过表达FasL参与诱导这一过程。然而,肝癌患者中凋亡、CD8⁺T细胞和Foxp3⁺T细胞之间的关系仍不清楚。本研究旨在探讨肝癌患者CD8⁺T淋巴细胞和Foxp3⁺T细胞中凋亡水平与Fas/FasL表达之间的相关性。
从肝癌患者和正常对照者的外周血中检测CD8⁺T细胞和CD3⁺Foxp3⁺T细胞,并进行多色流式细胞术检测。评估凋亡标志物(膜联蛋白V)在CD8⁺T细胞中的表达以及死亡受体Fas在CD8⁺T细胞中的表达,FasL在CD3⁺Foxp3⁺T细胞中的表达。采用酶联免疫吸附测定法检测肝癌患者血清中转化生长因子-β1(TGF-β1)水平。然后评估凋亡与Fas表达以及CD3⁺Foxp3⁺T细胞中FasL表达之间的关系。
肝癌患者中CD8⁺T细胞与膜联蛋白V结合的频率以及CD8⁺T细胞中Fas的表达均高于正常对照者,且凋亡的CD8⁺T细胞比例与其Fas表达相关。血清TGF-β1水平与CD3⁺Foxp3⁺T细胞呈负相关。
Fas/FasL相互作用可能导致肝癌患者CD8⁺T细胞过度更新,并降低抗肿瘤免疫反应。需要进一步在体外对Fas⁺CD8⁺T细胞凋亡诱导进行研究。