Increase of CD4 + CD25 + regulatory T-cells in the liver of patients with hepatocellular carcinoma

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.