title: Immunoregulation of dendritic and T cells by alpha-fetoprotein in patients with hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Department of Medicine II, University Hospital Freiburg, Hugstetter Strasse 55, D-79106, Freiburg, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Ritter
authors.forename: Mona Y
authors.initials: MY
authors.lastname: Ali
authors.forename: Christian F
authors.initials: CF
authors.lastname: Grimm
authors.forename: Robert
authors.initials: R
authors.lastname: Weth
authors.forename: Leonhard
authors.initials: L
authors.lastname: Mohr
authors.forename: Wulf O
authors.initials: WO
authors.lastname: Bocher
authors.forename: Katja
authors.initials: K
authors.lastname: Endrulat
authors.forename: Heiner
authors.initials: H
authors.lastname: Wedemeyer
authors.forename: Hubert E
authors.initials: HE
authors.lastname: Blum
authors.forename: Michael
authors.initials: M
authors.lastname: Geissler
mesh_terms: 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
chemical_list: D015703:Antigens, CD; D000509:alpha-Fetoproteins