Increased frequency and FOXP3 expression of human CD8+CD25High+ T lymphocytes and its relation to CD4 regulatory T cells in patients with hepatocellular carcinoma

Abstract The mechanism of action of CD8 + CD25 High+ FOXP3 + T cells in hepatocellular carcinoma (HCC) has not been fully understood. Herein, the role of CD8 + CD25 High+ FOXP3 + T cells in HCC was compared with that of CD4 + CD25 High+ FOXP3 + regulatory T cells (conventional Tregs). Thirty-five patients with HCC and twenty age and sex-matched healthy adults (controls) were enrolled. The percentage of CD8 + CD25 High+ FOXP3 + T cells and conventional Tregs in peripheral blood was measured by flow cytometry. Our results revealed that the percentage of peripheral CD8 + CD25 High+ FOXP3 + 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  + CD25 High+ T cells is higher than that of CD8 + CD25 low+ and CD8 + CD25 Negative T cells. The percentage of CD8 + CD25 High+ FOXP3 + 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 CD8 + CD25 High+ FOXP3 + T cells and conventional Tregs (R2 = 0.481, P  + CD25 High+ FOXP3 + T cells and conventional Tregs was significantly increased in HCC with multiple lesions compared with those with one or two lesions. In conclusion: CD8 + CD25 High+ FOXP3 + T cells similar to conventional Tregs might be used as biomarkers of HCC progression. Therapy targeting the peripherally expanded CD8 + CD25 High+ FOXP3 + T cells may provide a novel perspective for HCC treatment.