Assessment of Treg Cells CD4(+)CD25(+) in Chronic Cirrhotic Liver Disease and Hepatocellular Carcinoma Egyptian Patients

Background and Aims: Dysfunction of the host immune system in cancer patients can be due to a number of factors, including secretion of tumor-derived immunosuppressive factors or induction of immune tolerance against tumor-specific antigens. Several studies suggest that suppression of tumor-associated antigen reactivates lymphocytes by CD4+ CD25+ regulatory T (Treg) cells. This study was designed to evaluate whether CD4+CD25+ Treg cells in chronic liver disease and hepatocellular carcinoma (HCC) patients exhibit an expanded Treg pool and to correlate it with liver tumor markers and grading.

Methods: Blood samples were collected from 20 patients with cirrhotic liver disease (CLD), 15 HCC patients and 10 healthy control subjects. Alpha feto-protein (AFP), HBV and HCV antibodies were detected by EIA. HCV was confirmed by immunoblotting and RT-PCR. To evaluate HCC grading, abdominal ultrasound guided liver biopsy was done. Patients were categorized into moderately differentiated (grade II) and poorly differentiated (grade III) groups. Cytometric analysis of CD4+CD25+ Treg cells in PBMCs was performed using anti-CD3, anti-CD4, anti-CD25, anti-CD45RA, and IgG-isotype control (FITC and PE).

Results: Both CLD and HCC groups were 80% positive for HCV while only 20% of CLD and 11% of HCC patients were positive for HBV. The mean percentage of CD4+CD25+T cell population demonstrated a highly significant increase in comparing HCV to HCC patients [2.47±0.66 vs. 8.96±1.38 (P<0.001)] and when comparing both group to controls [1.15±0.5 (P<0.01)]. Nine HCC patients were in grade II while 6/15 were in grade III. Their mean CD4+CD25+ T cells percentage was 9.12±1.52 and 8.73±1.33, respectively. A negative correlation was found between mean CD4+CD25+ T cells percentage and AFP serum level in HCC patients (r=-0.923) while Treg cells with patients tumor grades (II and III) (r=0.474 and 0.582, respectively). CLD showed a significant correlation with AFP level (r= 0.962).

Conclusions: Tumor specific Treg cells may limit the efficacy of anti-tumor response. Treg cells correlate properly with the unique marker AFP and with tumor grades. Better understanding of the underlying mechanism of Treg regulation or of the strategy for controlling Treg cells may lead to effective HCV immunotherapy and enhancing immunity against cancer.