Decreased function of peripheral blood dendritic cells in patients with hepatocellular carcinoma with hepatitis B and C virus infection

Background: Tumour immunity does not seem to be induced effectively in tumo ur-bearing hosts, including in patients with hepatocellular carcinoma (HCC) . One possible reason is that function of dendritic cells (DC) is decreased in such hosts. Methods: We evaluated T cell stimulatory activity and interleukin (IL)-12 p roduction of DC and interferon (IFN)-gamma and IL-10 production of T cells of peripheral blood from 12 control individuals and 21 patients with chroni c hepatitis C virus (HCV) infection (six with chronic hepatitis (CH), eight with liver cirrhosis (LC) and 13 with HCC). Five hepatitis B virus (HBV)-i nfected patients with HCC were included as a disease control group. The DC were prepared by the culture of T cell-depleted populations of peripheral b lood mononuclear cells in the presence of granulocyte-macrophage colony sti mulating factor and IL-4 for a total of 11-12 days. The cytokine levels wer e assayed by ELISA. To test the stimulatory function of DC in T cell prolif eration, mytomycin C-treated DC were cultured with allogeneic T cells from a control. Results: When the T cell-stimulatory activity of DC was expressed as stimul ation index value of [H-3]-thymidine incorporation of T cells, the values w ere lower in HCV-infected HCC (2.6 +/- 1.8, P < 0.01) than in controls (5.5 +/- 2.0) and CH (5.0 +/- 1.3). Staphylococcus aureus Cowan 1-induced IL-12 production of DC was decreased in HCV-infected HCC (P < 0.001, P < 0.01 an d P < 0.05, respectively) compared with controls, CH and LC, while similar amounts of IL-10 were produced in patients and controls. Interleukin-10 and IFN-gamma production of T cells in response to anti-CD3 antibody or IL-12 were equivalent between patient groups and controls, respectively. Similarl y decreased DC function and normal T cell response were observed in HBV-inf ected HCC patients. Conclusions: These findings suggest that the depressed function of DC is as sociated with pathogenesis of HCC with HBV or HCV infection. (C) 2000 Black well Science Asia Pty Ltd.