Immunoregulation of dendritic and T cells by alpha-fetoprotein in patients with hepatocellular carcinoma.
OBJECTIVE
Novel immunotherapeutic and other strategies are being explored for the treatment of hepatocellular carcinoma (HCC). Alpha-fetoprotein (AFP) may be a target antigen for immunotherapy. Little is known, however, about the immunobiology of AFP. Therefore, the impact of AFP on dendritic cells (DC), CD4+ and CD8+ T cells was studied in detail.


METHODS
Immune cells from peripheral blood of 27 HCC patients were studied using FACS, ELISPOT, and proliferation assays.


RESULTS
The in vitro generation, maturation, and T cell stimulatory capacity of DCs were not altered by AFP up to concentrations of 20 microg/ml. Higher AFP concentrations (> 20 microg/ml) resulted in phenotypic changes on DCs without impairing their capacity to stimulate CD4+ T cells. Frequencies and function of DCs and AFP specific T cells were not reduced in HCC patients independent on serum AFP levels. Finally, T lymphocytic infiltrations in the liver were not dependent on AFP serum levels.


CONCLUSIONS
These studies clearly demonstrate that (i) DC-based immunotherapeutic approaches are a promising approach for HCC treatment and (ii) AFP-reactive T cell clones have not been deleted from the human T cell repertoire establishing AFP as a potential target for T cell based immunotherapy of HCC.
Ritter
Marcus
M
Department of Medicine II, University Hospital Freiburg, Hugstetter Strasse 55, D-79106, Freiburg, Germany.
Ali
Mona Y
MY
Grimm
Christian F
CF
Weth
Robert
R
Mohr
Leonhard
L
Bocher
Wulf O
WO
Endrulat
Katja
K
Wedemeyer
Heiner
H
Blum
Hubert E
HE
Geissler
Michael
M
D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D001773:Blood Cells; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000473:pathology; D016022:Case-Control Studies; D002455:Cell Division / Q000187:drug effects; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008113:Liver Neoplasms / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D013194:Staining and Labeling; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000276:immunology* / Q000494:pharmacology
D015703:Antigens, CD; D000509:alpha-Fetoproteins