title: Autologous dendritic cells loaded with apoptotic tumor cells induce T cell-mediated immune responses against breast cancer in vitro.
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.
authors.affiliation: Department of Cellular and Molecular Biotechnology, Institute of Biotechnology, Urmia University, Urmia, Iran. n.delirezh@urmia.ac.ir
authors.forename: Nowruz
authors.initials: N
authors.lastname: Delirezh
authors.forename: Seyed Mohammad
authors.initials: SM
authors.lastname: Moazzeni
authors.forename: Fazel
authors.initials: F
authors.lastname: Shokri
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Shokrgozar
authors.forename: Morteza
authors.initials: M
authors.lastname: Atri
authors.forename: Parviz
authors.initials: P
authors.lastname: Kokhaei
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000276:immunology; D001943:Breast Neoplasms / Q000276:immunology* / Q000628:therapy*; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005260:Female; D006801:Humans; D007111:Immunity, Cellular; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D020014:K562 Cells; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D015847:Interleukin-4; D007371:Interferon-gamma