Direct ex vivo analysis of dendritic cells in patients with hepatocellular carcinoma.
OBJECTIVE
To analyze the phenotype and function of dendritic cells (DC) from patients with hepatocellular carcinoma (HCC) in order to understand their role in this disease.


METHODS
Myeloid dendritic cells were enumerated in peripheral blood of HCC patients. CD80, CD83, CD86 and HLA-DR expression on naive and stimulated myeloid dendritic cells from peripheral blood were analyzed. Myeloid dendritic cells were isolated from peripheral blood and their function was tested. Phagocytosis was analyzed using FITC-dextran beads, peptide specific stimulation, the capacity to stimulate allogeneic T cells and secretion of cytokines upon poly dI:dC was tested.


RESULTS
Myeloid dendritic cells were reduced in patients with HCC. No differences in CD80, CD83, CD86 and HLA-DR expression were found on naive and stimulated myeloid dendritic cells from HCC patients and healthy controls. Normal phagocytosis or stimulation of peptide specific T cells was observed in contrast to an impaired allo-stimulatory capacity and a reduced IL-12 secretion.


CONCLUSIONS
Impaired IL-12 production of mDCs in patients could lead to an impaired stimulatory capacity of naive T cells suggesting that IL-12 directed therapies may enhance tumor specific immune responses in HCC patients.
Ormandy
Lars-A
LA
Department of Gastroenterology, Hepatology und Endocrinology, Medizinische Hochschule Hannover, Carl Neuberg Str. 1, 30625 Hannover, Germany.
Farber
Anatol
A
Cantz
Tobias
T
Petrykowska
Susanne
S
Wedemeyer
Heiner
H
Horning
Monique
M
Lehner
Frank
F
Manns
Michael-P
MP
Korangy
Firouzeh
F
Greten
Tim-F
TF
D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D018122:B7-1 Antigen / Q000032:analysis; D051940:B7-2 Antigen / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D016022:Case-Control Studies; D002648:Child; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology*; D003911:Dextrans / Q000493:pharmacokinetics; D005260:Female; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D018664:Interleukin-12 / Q000378:metabolism* / Q000502:physiology; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D010587:Phagocytosis / Q000502:physiology; D011070:Poly I-C / Q000494:pharmacology; D013601:T-Lymphocytes / Q000473:pathology / Q000502:physiology; D000097802:CD83 Antigen
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D016207:Cytokines; D003911:Dextrans; D016650:Fluorescein-5-isothiocyanate; D006684:HLA-DR Antigens; D007136:Immunoglobulins; D018664:Interleukin-12; D008562:Membrane Glycoproteins; D011070:Poly I-C; D000097802:CD83 Antigen; C015219:fluorescein isothiocyanate dextran