Dendritic cells with immature phenotype and defective function in the peripheral blood from patients with hepatocellular carcinoma.
OBJECTIVE
Defects and dysfunctions in antigen-presenting dendritic cells have been shown during carcinogenesis. The phenotype and function of dendritic cells have been studied in patients with hepatocellular carcinoma to explore the possibility of dendritic cell-based immune therapy in hepatocellular carcinoma.


METHODS
The stimulatory capacity of dendritic cells in allogenic mixed leukocytes 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 carcinoma, 10 patients with liver cirrhosis and 10 normal controls were compared.


RESULTS
Dendritic cells from hepatocellular carcinoma had significantly lower capacity to stimulate allogenic T cells in allogenic mixed leukocytes reaction compared with dendritic cells from liver cirrhosis and normal controls (p<0.05). Dendritic cells from hepatocellular carcinoma expressed significantly lower levels of HLA DR and induced decreased amounts of interleukin-12 compared with dendritic cells from normal controls (p<0.05). On the other hand, dendritic cells from hepatocellular carcinoma produced significantly higher levels of nitric oxide and tumor necrosis factor-a compared with dendritic cells from liver cirrhosis and normal controls (p<0.05). The uptake of fluorescein isothiocyanate-labeled dextran revealed an immature phenotype of dendritic cells from hepatocellular carcinoma compared with dendritic cells from liver cirrhosis (p<0.05).


CONCLUSIONS
The results of this study on the function of dendritic cells in hepatocellular carcinoma, and the prevalence of immature dendritic cells in hepatocellular carcinoma in the microenvironment of high levels of inflammatory cytokines indicate a specific defect of dendritic cell maturation during hepatocarcinogenesis. These data show that induction of dendritic cell maturation might be an approach to dendritic cell-based immune therapy during hepatocellular carcinoma.
Ninomiya
T
T
Third Department of Internal Medicine, Ehime University School of Medicine, Japan.
Akbar
S M
SM
Masumoto
T
T
Horiike
N
N
Onji
M
M
D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000473:pathology*; D016022:Case-Control Studies; D002453:Cell Cycle; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000473:pathology*; D008113:Liver Neoplasms / Q000097:blood / Q000473:pathology*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood; D010641:Phenotype
D015415:Biomarkers; D016207:Cytokines; D009569:Nitric Oxide