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J Hepatol. 2006 Aug;45(2):254-62. Epub 2006 Mar 9.

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

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Division of Gastroenterology and Hepatology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.



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.


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.


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.


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.

[Indexed for MEDLINE]

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