Immunoregulation of dendritic and T cells by alpha-fetoprotein in patients with hepatocellular carcinoma

PMID: 15582134
Journal: Journal of hepatology (volume: 41, issue: 6, J. Hepatol. 2004 Dec;41(6):999-1007)
Published: 2004-12-01

Ritter M, Ali MY, Grimm CF, Weth R, Mohr L, Bocher WO, Endrulat K, Wedemeyer H, Blum HE, Geissler M


BACKGROUND/AIMS: 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.