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 tumour‐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 production of DC and interferon (IFN)‐γ and IL‐10 production of T cells of peripheral blood from 12 control individuals and 21 patients with chronic hepatitis C virus (HCV) infection (six with chronic hepatitis (CH), eight with liver cirrhosis (LC) and 13 with HCC). Five hepatitis B virus (HBV)‐infected patients with HCC were included as a disease control group. The DC were prepared by the culture of T cell‐depleted populations of peripheral blood mononuclear cells in the presence of granulocyte‐macrophage colony stimulating factor and IL‐4 for a total of 11–12 days. The cytokine levels were assayed by ELISA. To test the stimulatory function of DC in T cell proliferation, 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 stimulation index value of [3H]‐thymidine incorporation of T cells, the values were 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 and 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‐γ production of T cells in response to anti‐CD3 antibody or IL‐12 were equivalent between patient groups and controls, respectively. Similarly decreased DC function and normal T cell response were observed in HBV‐infected HCC patients. Conclusions : These findings suggest that the depressed function of DC is associated with pathogenesis of HCC with HBV or HCV infection.