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急性髓系白血病原始细胞产生的树突状细胞(DC)与T细胞在混合淋巴细胞培养(MLC)中的细胞因子释放模式有助于预测抗白血病T细胞反应及患者对免疫治疗的反应。

Cytokine Release Patterns in Mixed Lymphocyte Culture (MLC) of T-Cells with Dendritic Cells (DC) Generated from AML Blasts Contribute to Predict anti-Leukaemic T-Cell Reactions and Patients' Response to Immunotherapy.

作者信息

Fischbacher Dorothea, Merle Marion, Liepert Anja, Grabrucker Christine, Kroell Tanja, Kremser Andreas, Dreyßig Julia, Freudenreich Markus, Schuster Friedhelm, Borkhardt Arndt, Kraemer Doris, Koehne Claus-Henning, Kolb Hans-Jochem, Schmid Christoph, Schmetzer Helga Maria

机构信息

a Department for Haematopoietic Transplantations , University Hospital of Munich , Munich , Germany.

b Department for pediatric Haematology and Oncology , University Hospital of Düsseldorf , Düsseldorf , Germany.

出版信息

Cell Commun Adhes. 2015 Apr-Dec;22(2-6):49-65. doi: 10.1080/15419061.2016.1223634. Epub 2016 Sep 7.

DOI:10.1080/15419061.2016.1223634
PMID:27602789
Abstract

To enlighten interactions between autologous, allogeneic or T-cells from patients after stem cell transplantation with leukaemia-derived-dendritic-cells containing dendritic cells or blast containing mononuclear cells (n = 21, respectively), we determined cytokine-concentrations (interleukin 2, 4, 6, 10, tumor-necrosis-factor-α, interferon-γ) in supernatants of mixed-lymphocyte-culture and in serum (n = 16) of 20 patients with acute myeloid leukaemia and three patients with myelodysplastic syndromes by cytometric-bead-assay. We correlated our data with lytic capabilities of stimulated T-cells in a fluorolysis-assay and clinical data: Dendritic-cell-/mononuclear-cell-stimulation of T-cells resulted in increased cytokine-levels in culture-medium compared to serum. There were no significant differences between cytokine-patterns of cases with/without lytic T-cell-activity, response to immunotherapy (stem cell transplantation/donor-lymphocyte-infusion) or graft-versus-host-disease. However, some predictive cytokine-cut-off-values for antileukaemic T-cell-activity, patients' response to immunotherapy and graft-versus-host-disease could be defined. Cytokine-profiles alone, without functional assays, are no useful tool to predict antileukaemic T-cell-function, although they can indicate lytic T-cell-activity, patients' response to immunotherapy and graft-versus-host-disease.

摘要

为了阐明自体、异体或干细胞移植后患者的T细胞与含有树突状细胞的白血病来源树突状细胞或含有原始细胞的单核细胞(分别为n = 21)之间的相互作用,我们通过细胞计数珠分析法测定了20例急性髓系白血病患者和3例骨髓增生异常综合征患者的混合淋巴细胞培养上清液和血清(n = 16)中的细胞因子浓度(白细胞介素2、4、6、10、肿瘤坏死因子-α、干扰素-γ)。我们将我们的数据与荧光溶解试验中刺激T细胞的裂解能力以及临床数据相关联:与血清相比,树突状细胞/单核细胞对T细胞的刺激导致培养基中细胞因子水平升高。在有/无裂解性T细胞活性、对免疫疗法(干细胞移植/供体淋巴细胞输注)的反应或移植物抗宿主病的病例的细胞因子模式之间没有显著差异。然而,可以定义一些抗白血病T细胞活性、患者对免疫疗法的反应和移植物抗宿主病的预测性细胞因子临界值。仅细胞因子谱,在没有功能测定的情况下,不是预测抗白血病T细胞功能的有用工具,尽管它们可以指示裂解性T细胞活性、患者对免疫疗法的反应和移植物抗宿主病。

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