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题目:: induction of antitumor DEC-205 CD11c cells in a murine neuroblastoma model by co-stimulation with doxorubicin, lipopolysaccharide and interleukin-4.
作者:: Inoue(Seiichiro),Setoyama(Yumiko),Beck(Yoshifumi),Kitagawa(Daiki),Odaka(Akio)
状态:: 发布时间2016-02-12 , 更新时间 2016-02-14
期刊:: Biomed Rep
摘要:: The antigen-presenting capacity of specific cells and tumor immunogenicity involved in innate cellular immunity are important for initiating an antitumor response to advanced neuroblastoma. The present study was performed to establish a method of producing antigen-presenting cells that induced an immune response to murine neuroblastoma cells through culture with neuroblastoma cells that had undergone immunogenic cell death. Immunogenic death of neuro-2a murine neuroblastoma cells was induced by exposure to doxorubicin. Mouse bone marrow cells were cultured in medium containing granulocyte-macrophage colony-stimulating factor, followed by the addition of doxorubicin-treated neuro-2a cells to the culture with or without lipopolysaccharide (LPS) and/or interleukin-4. Subsequently, cluster of differentiation (CD) 8α lymphocytes were co-cultured with neuro-2a cells and the adherent bone marrow cells obtained by the above procedure to evaluate CD8α lymphocyte proliferation and interferon-γ production. Furthermore, the surface antigen profile of adherent bone marrow cells was analyzed by flow cytometry. When adherent bone marrow cells were treated with LPS and/or interleukin-4, followed by co-culture with CD8α lymphocytes and neuro-2a cells, interferon-γ production by the CD8α cells increased in response to anti-CD3/CD28 antibody stimulation. CD11c major histocompatibility complex II (MHC II) double-positive cells were increased among adherent cells derived from cultured bone marrow cells. These cells were positive for DEC-205, but not CD8α. These findings suggest that co-culture of bone marrow-derived cells with tumor cells (that have undergone immunogenic death by exposure to doxorubicin) plus stimulation by LPS and interleukin-4 induces antigen-presenting cells that can evoke an immune response to neuroblastoma. Bone marrow-derived DEC-205 CD11c MHC II dendritic cells are key antigen-presenting cells in the induction of an immune response following phagocytosis of doxorubicin-treated neuroblastoma cells.
语言:: eng
DOI:

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