356 RECENT PROGRESS IN MANAGEMENT OF HEPATOCELLULAR CARCINOMA DIAGNOSED DURING SURVEILLANCE IN JAPAN

Background and Aims: Chronic hepatitis B virus (HBV) infection is the key cause of hepatocellular carcinoma (HCC) in Asian.Recent studies showed regulatory T cells (Treg) are increased and linked to impaired immune response in patients with chronic hepatitis B (CHB).Treg can modulate the function and expansion of viral or tumor-specific CD8+ cells.Evaluating whether the Treg involved in immunopathogenesis from chronic hepatitis B progressed to HCC will help us to gain more insight in immunopathogenesis of HCC.Methods: We investigated properties of Treg from 47 HCC patients with or without chronic hepatitis B virus (HBV) infection, 30 CHB patients and 20 healthy donors by flow cytometric, immunohistochemical, and immunosuppressive assays.Immunosuppression to anti-tumor immune response induced by HCC tumor antigen (NY-ESO-1 or MAGE-A3) was evaluated in circulating and liver resident Tregs of CHB patients.Furthermore, evaluating the influence of HBV infected to Treg using the normal liver cells line, liver cells line with HBV integrated expression (HepG2.2.15) and hepatocellular carcinoma (HepG2, Huh7) co-cultured with peripheral blood mononuclear cells in vitro.Results: Treg increased in circulating and liver resident in CHB and HCC patients.Especially in peripheral blood of HCC patients with HBV infection the increasing of Treg is obvious.The increasing Treg in CHB patients suppressed the sepcific immune response induced by HCC tumor antigen (NY-ESO-1 or MAGE-A3) as well as HBV antigen.Liver cells line with HBV integrated expression, hepatocellular carcinoma cells lines can increase expansion of Foxp3, CTLA-4, GITR, and CD103 and function of Treg in vitro which may be induced by TGF-beta1.The increasing Treg co-cultured with liver cells line with HBV integrated expression can also suppress the tumor antigen sepcific immune response induced by HCC tumor antigen (NY-ESO-1 or MAGE-A3).Conclusions: These findings suggest that Treg in CHB patients maybe involved in immunopathogenesis from chronic hepatitis B progressed to hepatocellular carcinoma.