Background/Aims:The immune response to tumor-specific antigens is typically unable to control the growth and spread of malignant cells.Accumulating evidence indicates that the suppressive effects of CD4+ CD25+ regulatory T-cells are at least partially responsible for the failure of immune-mediated elimination of tumor cells.Methods:We have studied 25 patients with hepatocellular carcinoma(HCC) .The liver tissues with HCC were separated into the marginal region of tumor(peri-tumor region) and the non-tumor region distant from the tumor.CD4+ CD25+ T-cells were quantified in the blood and the liver by flow cytometry and immunohistochemistry,and their effect on T-cell proliferation and activation was determined.Results:We found a significant increase in both the proportion and absolute numbers of CD4+ CD25+ T-cells in the peri-tumor regions,but not in unaffected areas(9.5 ± 4.5 vs.4.6 ± 2.8%,P = 0.011) .CD4+ CD25+ T-cells isolated from peri-tumor regions displayed phenotype markers characteristic of regulatory T-cells,and expressed Foxp3 mRNA.CD8+ T-cells in peri-tumor regions were inversely proportional to CD4+ CD25+ T-cells in the same region(P < 0.001) .Moreover,isolated CD4+ CD25+ T-cells inhibited autologous CD8+ T-cell proliferation.Conclusions:Our results suggest that CD4+ CD25+ T-cells in the marginal region of HCC may play a critical role in controlling CD8+ cytotoxic T-cell activity and,thereby,contribute to the progression of HCC.
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