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肝癌患者外周血 CD8CD25T 淋巴细胞频数及其 FOXP3 表达的变化及其与 CD4 调节性 T 细胞的关系。

Increased frequency and FOXP3 expression of human CD8CD25 T lymphocytes and its relation to CD4 regulatory T cells in patients with hepatocellular carcinoma.

机构信息

Department of Clinical Pathology, South Egypt Cancer Institute, Assiut, Egypt.

Department of Microbiology and Immunology, Faculty of Medicine, Assiut University, Egypt.

出版信息

Hum Immunol. 2019 Jul;80(7):510-516. doi: 10.1016/j.humimm.2019.03.014. Epub 2019 Mar 20.

DOI:10.1016/j.humimm.2019.03.014
PMID:30904437
Abstract

The mechanism of action of CD8CD25FOXP3 T cells in hepatocellular carcinoma (HCC) has not been fully understood. Herein, the role of CD8CD25FOXP3 T cells in HCC was compared with that of CD4CD25FOXP3 regulatory T cells (conventional Tregs). Thirty-five patients with HCC and twenty age and sex-matched healthy adults (controls) were enrolled. The percentage of CD8CD25FOXP3 T cells and conventional Tregs in peripheral blood was measured by flow cytometry. Our results revealed that the percentage of peripheral CD8CD25FOXP3 T cells in HCC patients was significantly higher than controls (P = 0.005). The conventional Tregs showed the same trend with a higher level in HCC than controls (P < 0.0001). FOXP3 expression of CD8CD25 T cells is higher than that of CD8CD25 and CD8CD25 T cells. The percentage of CD8CD25FOXP3 T cells positively correlated with that of conventional Tregs in HCC patients but not in controls. The higher alpha-fetoprotein positively correlated with the higher CD8CD25FOXP3 T cells and conventional Tregs (R2 = 0.481, P < 0.0001 and R2 = 0.249, P = 0.001, respectively). The frequency of both CD8CD25FOXP3 T cells and conventional Tregs was significantly increased in HCC with multiple lesions compared with those with one or two lesions. In conclusion: CD8CD25FOXP3 T cells similar to conventional Tregs might be used as biomarkers of HCC progression. Therapy targeting the peripherally expanded CD8CD25FOXP3 T cells may provide a novel perspective for HCC treatment.

摘要

CD8CD25FOXP3 T 细胞在肝细胞癌 (HCC) 中的作用机制尚未完全阐明。在此,将 CD8CD25FOXP3 T 细胞在 HCC 中的作用与 CD4CD25FOXP3 调节性 T 细胞(传统 Tregs)进行了比较。纳入 35 例 HCC 患者和 20 名年龄和性别匹配的健康成年人(对照组)。采用流式细胞术检测外周血 CD8CD25FOXP3 T 细胞和传统 Tregs 的百分比。结果显示,HCC 患者外周血 CD8CD25FOXP3 T 细胞的百分比明显高于对照组(P=0.005)。传统 Tregs 也呈现出同样的趋势,HCC 患者中水平高于对照组(P<0.0001)。CD8CD25FOXP3 T 细胞的 FOXP3 表达高于 CD8CD25 和 CD8CD25FOXP3 T 细胞。HCC 患者中 CD8CD25FOXP3 T 细胞的百分比与传统 Tregs 呈正相关,但在对照组中则无相关性。较高的甲胎蛋白与较高的 CD8CD25FOXP3 T 细胞和传统 Tregs 呈正相关(R2=0.481,P<0.0001 和 R2=0.249,P=0.001)。与单发或双发病变相比,多发病变 HCC 患者中 CD8CD25FOXP3 T 细胞和传统 Tregs 的频率均显著增加。总之,与传统 Tregs 相似的 CD8CD25FOXP3 T 细胞可能作为 HCC 进展的生物标志物。针对外周扩增的 CD8CD25FOXP3 T 细胞的治疗可能为 HCC 治疗提供新视角。

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