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 < 0.0001). FOXP3 expression of CD8⁺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 < 0.0001 and R2 = 0.249, P = 0.001, respectively). The frequency of both CD8⁺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.

Keywords: CD8(+)CD25(High+)FOXP3(+)T cells; Conventional CD4(+) regulatory T cells; Hepatocellular carcinoma.