Ex vivo induction of antitumor DEC-205+ CD11c+ cells in a murine neuroblastoma model by co-stimulation with doxorubicin, lipopolysaccharide and interleukin-4.
Ex vivo induction of antitumor DEC-205+ CD11c+ cells in a murine neuroblastoma model by co-stimulation with doxorubicin, lipopolysaccharide and interleukin-4.
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通过与阿霉素、脂多糖和白细胞介素 4 共刺激，在小鼠神经母细胞瘤模型中离体诱导抗肿瘤 DEC-205 CD11c 细胞。
DOI：
10.3892/br.2015.546
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发表时间：
2016
影响因子：
2.3
通讯作者：
A. Odaka
中科院分区：
文献类型：
--
作者：
Seiichiro Inoue;Y. Setoyama;Y. Beck;Daiki Kitagawa;A. Odaka
参与先天细胞免疫的特定细胞的抗原提呈能力和肿瘤免疫原性对于启动对晚期神经母细胞瘤的抗肿瘤反应是重要的。本研究旨在建立一种产生抗原提呈细胞的方法，通过与经历了免疫原性细胞死亡的神经母细胞瘤细胞培养来诱导对小鼠神经母细胞瘤细胞的免疫应答。用阿霉素诱导小鼠神经母细胞瘤细胞的免疫原性死亡。小鼠骨髓细胞在含有粒细胞-巨噬细胞集落刺激因子的培养液中培养，然后在含有或不含有脂多糖和/或白介素4的培养液中加入阿霉素处理的Neo-2a细胞。将分化集落(CD)8α+淋巴细胞与Neu-2a细胞和贴壁的骨髓细胞共培养，检测CD8α+淋巴细胞的增殖和干扰素-γ的产生。用流式细胞仪分析贴壁的骨髓细胞的表面抗原分布。当贴壁的骨髓细胞经脂多糖和/或白介素4处理后，与CD8CD3CD28抗体刺激的α+细胞和神经2a细胞共培养时，CD8CD3CD28抗体刺激的CD8CD8γ+细胞产生干扰素-α。骨髓细胞来源的贴壁细胞中CD11c主要组织相容性复合体II(MHC II)双阳性细胞增多。这些细胞表达DEC205，但不表达CD8α。这些发现表明，骨髓来源的细胞与肿瘤细胞(因接触阿霉素而发生免疫性死亡)再加上脂多糖和白介素4的刺激，可以诱导抗原提呈细胞，从而激发对神经母细胞瘤的免疫反应。骨髓来源的DEC-205+CD11c+MHC II+树突状细胞是阿霉素处理的神经母细胞瘤细胞吞噬后诱导免疫应答的关键抗原提呈细胞。
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.
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影响因子：
45.3
作者：
Navid, Fariba;Sondel, Paul M.;Santana, Victor M.
通讯作者：
Santana, Victor M.
DOI：
10.1056/nejmoa0911123
发表时间：
2010-09-30
期刊：
The New England journal of medicine
影响因子：
--
作者：
Yu AL;Gilman AL;Ozkaynak MF;London WB;Kreissman SG;Chen HX;Smith M;Anderson B;Villablanca JG;Matthay KK;Shimada H;Grupp SA;Seeger R;Reynolds CP;Buxton A;Reisfeld RA;Gillies SD;Cohn SL;Maris JM;Sondel PM;Children's Oncology Group
通讯作者：
Children's Oncology Group
影响因子：
4.3
作者：
INABA, K;SWIGGARD, WJ;STEINMAN, RM
通讯作者：
STEINMAN, RM
DOI：
10.1056/nejmra0804577
发表时间：
2010-06-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Maris JM
通讯作者：
Maris JM