Increased Frequency of CD4+CD25highFoxP3+ Regulatory T Cells in Patients with Hepatocellular Carcinoma

Accumulating evidence suggests regulatory T cells (Tregs) are associated with impaired antitumor responses. However, the relationship between the CD4(+)CD25(high)FoxP3(+) Treg and hepatocellular carcinoma (HCC) has not been well investigated. Levels of CD4(+)CD25(high)FoxP3(+) Tregs in peripheral blood mononuclear cells (PBMCs) from HCC patients and healthy donors, tumor infiltrating lymphocytes (TILs) extracted from HCC, and hepatic lymphocytes extracted from resected liver were measured by flow cytometry, and their effects on T-cell proliferation was determined by H-3-thymidine incorporation. Serum levels of interleukin (IL)-10 and transforming growth factor (TGF)-beta 1 were measured by enzyme linked immunosorbent assay. The frequency of Tregs in PBMCs from HCC patients was higher than that from healthy donors. Similarly, the frequency of Tregs in TILs was higher than that of hepatic lymphocytes. On the other hand, the H-3-thymidine uptake by TILs and PBMCs from HCC patients was decreased drastically when compared to the counterparts from normal controls. Furthermore, serum IL-10 and TGF-beta 1 levels increased significantly in HCC patients when compared to the healthy donors. This study identified an increased frequency of CD4(+)CD25(high)FoxP3(+) Tregs in patients with HCC. The elevated serum IL-10, TGF-beta 1 levels also correlated with impaired antitumor responses in these patients. Further effort is needed to establish new immunotherapeutic strategies designed to modulate Tregs to promote a competent antitumor response.