Autologous dendritic cells loaded with apoptotic tumor cells induce T cell-mediated immune responses against breast cancer in vitro

• Published in: Cellular immunology Vol. 257; no. 1; pp. 23 - 31
• Main Authors: Delirezh, Nowruz, Moazzeni, Seyed Mohammad, Shokri, Fazel, Shokrgozar, Mohammad Ali, Atri, Morteza, Kokhaei, Parviz
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 2009
• Subjects: Adult; Apoptosis - immunology; Apoptotic Tumor cells; Breast cancer; Breast Neoplasms - immunology; Breast Neoplasms - therapy; Cell Line, Tumor; Cytotoxicity, Immunologic; Dendritic cells; Dendritic Cells - immunology; Dendritic Cells - transplantation; Female; Humans; Immunity, Cellular; Immunotherapy, Adoptive; In vitro; Interferon-gamma - biosynthesis; Interferon-gamma - immunology; Interleukin-4 - biosynthesis; Interleukin-4 - immunology; K562 Cells; Medicin och hälsovetenskap; Middle Aged; T cell response; T-Lymphocytes, Cytotoxic - immunology; Breast cancer; Apoptotic Tumor cells; Dendritic cells; In vitro; T cell response
• ISSN: 0008-8749; 1090-2163; 1090-2163
• DOI: 10.1016/j.cellimm.2009.02.002

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 [ 3H] thymidine uptake and specific cytotoxic activity of tumor antigen-primed T cells after three rounds of weekly stimulation by flow cytometry. Interferon-γ (IFN-γ) and interleukin-4 (IL-4) cytokine release assay was carried out 24 h 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-γ and IL-4 in response to re-stimulation by antigen-pulsed DCs, but were dominated by IFN-γ 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.