Department of Clinical Pathology, South Egypt Cancer Institute, Assiut, Egypt.
Department of Microbiology and Immunology, Faculty of Medicine, Assiut University, Egypt.
Hum Immunol. 2019 Jul;80(7):510-516. doi: 10.1016/j.humimm.2019.03.014. Epub 2019 Mar 20.
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.
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。