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.
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.
Authors: Angela D Pardee; Hiroshi Yano; Aliyah M Weinstein; Aaron A K Ponce; Alexander D Ethridge; Daniel P Normolle; Lazar Vujanovic; Gerald J Mizejewski; Simon C Watkins; Lisa H Butterfield Journal: J Immunother Cancer Date: 2015-07-21 Impact factor: 13.751