Dendritic cells with immature phenotype and defective function in the peripheral blood from patients with hepatocellular carcinoma

Background/Aims: Defects and dysfunctions in antigen-presenting dendritic c ells have been shown during carcinogenesis. The phenotype and function of d endritic cells have been studied in patients with hepatocellular carcinoma to explore the possibility of dendritic cell-based immune therapy in hepato cellular carcinoma. Methods: The stimulatory capacity of dendritic cells in allogenic mixed leu kocytes reaction, the expression of surface makers on dendritic cells, the production of cytokines and nitric oxide by dendritic cells and the levels of maturation of dendritic cells from 17 patients with hepatocellular carci noma, 10 patients with liver cirrhosis and 10 normal controls were compared . Result: Dendritic cells from hepatocellular carcinoma had significantly low er capacity to stimulate allogenic T cells in allogenic mixed leukocytes re action compared with dendritic cells from liver cirrhosis and normal contro ls (p<0.05). Dendritic cells from hepatocellular carcinoma expressed signif icantly lower levels of HLA DR and induced decreased amounts of interleukin -12 compared with dendritic cells from normal controls (p<0.05), On the oth er hand, dendritic cells from hepatocellular carcinoma produced significant ly higher levels of nitric oxide and tumor necrosis factor-alpha compared w ith dendritic cells from liver cirrhosis and normal controls (p<0.05). The uptake of fluorescein isothiocyanate-labeled dextran revealed an immature p henotype of dendritic cells from hepatocellular carcinoma compared with den dritic cells from liver cirrhosis (p<0.05). Conclusion: The results of this study on the function of dendritic cells in hepatocellular carcinoma, and the prevalence of immature dendritic cells i n hepatocellular carcinoma in the microenvironment of high levels of inflam matory cytokines indicate a specific defect of dendritic cell maturation du ring hepatocarcinogenesis. These data show that induction of dendritic cell maturation might be an approach to dendritic cell-based immune therapy dur ing hepatocellular carcinoma.