Evaluation of CD4+CD25+ regulatory T cells in patients with hepatocellular carcinoma and liver cirrhosis

The emergence of a Tumor results from the disruption of cell growth regulation as well as from failure of the host to provoke a sufficient immunological anti-tumor response.Regulatory T cells CD4+CD25+ (Tregs) play an important role in maintaining peripheral self-tolerance, thus preventing autoimmune pathologies. However, in certain situations Tregs can impair effective immunity to some pathogens and tumor cells. Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death in the world, and in developed countries it is expected to continue to increase because of the epidemic of chronic hepatitis C virus (HCV) infection. Previous studies also showed that Tregs infiltrating HCC tumors were an indicator of poor prognosis.
 
Aim: of this study was to evaluate CD4+CD25+ Treg cells in patients with HCC and liver cirrhosis and their correlation with liver  tumor markers  and  grading.
 
Patients and Methods: The study included 30 patients, 15 patients had HCC (group I) and 15 were cirrhotic patients (group II). In addition, 10 healthy subjects were used as controls. All patients were subjected to clinical examination and laboratory investigations including liver function tests, hepatitis B markers (HBs Ag, HBeAg and HBc-Ab) and HCV antibodies were detected by ELISA. and Bilharzial Abs by indirect hemagglutination test. CD4⁺CD25⁺ Tcells were quantified in the blood by flow cytometry, alpha feto protein by Cobas e 411, To evaluate HCC grading ,abdominal sonography, C.T.and liver biopsy were done. Patients were categorized into mildely differentiated (grad 1), moderately differentiated (grad 11) and poorly differentiated (grad 111).
 
Results: There were significant increased in serum AFP, and CD4⁺CD25⁺% in patients with HCC, and in patients with liver cirrhosis when compared to control group (p<0.05), and highly significant increased in AFP, and CD4+CD25+ % in patients with HCC when compared to patients with liver cirrhosis (p<0.001). In HCC patients there were 2 patients (13.3%) of grade I, 10 patients (66.7%) of grade II  and 3 patients (20% )of grade III .Regression analysis showed negative significant correlation between CD4⁺CD25⁺% and ALT (p<0.05, r=-0.51), and positive significant correlation between CD4+CD25+  and AFP (p<0.05, r=0.41) among patients with HCC.  Also there was positive correlation between CD4+CD25+  and ALT (p<0.05, r =0.46) among patients with liver cirrhosis.
 
Conclusion: Our finding suggests that increased frequency of Treg cells might play a role in modulation of the immune response in HCC and liver cirrhosis, through limitation of the efficacy of anti-tumor response. Treg cells correlate properly with AFP and with tumor grades; this may play a major role in the inflammatory activity in the liver. Better understanding of the underlying mechanism of Tregs regulation may help to find immunotherapy  for HCC and enhancing immunity  against cancer.