Immune responses of dendritic cells loaded with antigens from apoptotic cholangiocarcinoma cells caused by γ-irradation

Abstract

To investigate the induction cytotoxic T cells (CTLs) with antitumor activity and therapeutic efficacy after dendritic cells (DCs) acquired antigen from apoptotic cholangiocarcinoma cells caused by γ-irradiation. DCs from peripheral blood mononuclear cells (PBMC) that maintain the antigen capturing and processing capacity charateristic of immature cells have been established in vitro, using granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin-4 (IL-4). Then, in cholangiocarcinoma cells apoptosis was induced by γ-irradiation. The experimental groups were as follows: (1) coculture of DCs and apoptotic cancer cells and T cells; (2) coculture of DCs and necrotic cancer cells and T cells; (3) coculture of DCs, cultured cancer cell and T cells. They are cocultured for 7 days. DCs and T cells were riched, isolated and their antitumor response was tested. The cells had typical dendritic morphology, expressed high levels of CD1a and B7, acquired antigen from apoptotic cells caused by γ-irradiation and induced an increased T cell stimulatory capacity in mixed lymphocyte reactions (MLR). DCs obtained from PBMCs using GM-CSF and IL-4 can efficiently present antigen derived from apoptotic cells caused by γ-irradiation and efficiently induce T cells. This strategy, therefore, may present an effective approach to transduce DCs with antigen.