ABSTRACT
Recent studies have suggested that CD4[+] CD25[+] regulatory T cells [Tregs] are increased and linked to compromised immune responses in patients with hepatocellular carcinoma [HCC]. The forkhead/winged helix transcription factor [FOXP3] is a useful marker for the presence of Tregs as it is required for their development and function. Failure of host antitumor immunity may be caused by exaggerated suppression of tumor-associated antigen-reactive lymphocytes mediated by Treg cells; however, definitive evidence that Treg cells have an immunopathological role in human cancer is lacking. This study attempted to characterize CD4[+] CD25[+] FOXP3 Treg cells in peripheral blood of HCV and HCV related HCC patients and to understand how the Treg cells affect immune responses and contribute to disease progression. A total of 80 patients, 30 with HCV-related HCC, 25 with chronic hepatitis C virus [CHC] infection 25 HCV-related liver cirrhosis [LC] patients and 20 normal controls were enrolled randomly. Flow cytometric assay for quantification of CD4[+] CD25[+] T cells and real time PCR assay for analysis of FOXP3 were used. Our study showed that the frequency of Treg cells was significantly increased in HCC patients compared with controls, CHC and cirrhotic patients [p<0.001]. However, the frequency of Treg cells was not significantly different in CHC and cirrhotic patients, which suggests that they play a central role in tumor immunity. In addition, the level of Treg cells in peripheral blood of HCC patients was significantly higher with the extent of tumor burden [large tumor size, increased number. unclear margin and vascular involvement]. Our results suggest that CD4[+] CD25[+] FOXP3 Treg cells may impair the effector function of T cells in HCC patients, promote disease progression and represent both a potential prognostic marker and a therapeutic target for HCV-related HCC individuals. A better understanding of the mechanisms of the Treg increase in HCC may allow for future immunotherapeutic and diagnostic opportunities in this population