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  • Title: Autologous dendritic cells loaded with apoptotic tumor cells induce T cell-mediated immune responses against breast cancer in vitro.
    Author: Delirezh N, Moazzeni SM, Shokri F, Shokrgozar MA, Atri M, Kokhaei P.
    Journal: Cell Immunol; 2009; 257(1-2):23-31. PubMed ID: 19306994.
    Abstract:
    Dendritic cell (DCs) based immunotherapy has received increased interest in the treatment of specific malignancies including breast cancer. In this in vitro study, T cell responses, which are induced by monocyte-derived DCs pulsed with apoptotic breast tumor cells (ApTC), were analyzed in terms of proliferation, specific cytotoxicity, and cytokine release. Nylon wool-enriched T lymphocytes from five patients with breast cancer stimulated with monocyte-derived DCs pulsed with apoptotic tumor cells in vitro and their proliferation response were analyzed by [(3)H] thymidine uptake and specific cytotoxic activity of tumor antigen-primed T cells after three rounds of weekly stimulation by flow cytometry. Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) cytokine release assay was carried out 24h after the last stimulation. The supernatant from primed T cells was collected and analyzed using commercially available ELISA kits. T cell proliferation assays revealed that DCs pulsed with apoptotic tumor cell could stimulate an autologous T cell proliferation response with stimulation indices of 5-21. The T cell-mediated cytotoxicity assay demonstrated that tumor antigen-primed T cells could kill significantly more autologous tumor cells than normal cells (P<0.05). These cells had variable amounts of cytotoxic activity against K562 cells. Primed T cells released both IFN-gamma and IL-4 in response to re-stimulation by antigen-pulsed DCs, but were dominated by IFN-gamma production in two out of five patients and IL-4 production in three out of five patients. In conclusion, our results suggested that DCs pulsed with apoptotic breast tumor cells could elicit effective specific antitumor T cell responses in vitro. Therefore, vaccination with DCs pulsed with apoptotic tumor cells may be considered as a novel strategy for immunotherapy of patients with breast cancer refractory to standard modalities.
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