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Conversion of AML-blasts to leukemia-derived dendritic cells (DCleu) in ‘DC-culture-media’ shifts correlations of released chemokines with antileukemic T-cell reactions
Immunobiology ( IF 2.8 ) Pub Date : 2021-03-20 , DOI: 10.1016/j.imbio.2021.152088
M Merle 1 , D Fischbacher 1 , A Liepert 1 , C Grabrucker 1 , T Kroell 1 , A Kremser 1 , J Dreyssig 1 , M Freudenreich 1 , F Schuster 2 , A Borkhardt 2 , D Kraemer 3 , C-H Koehne 3 , H J Kolb 4 , C Schmid 5 , H M Schmetzer 4
Affiliation  

Dendritic cells (DC) and T-cells are mediators of CTL-responses. Autologous (from patients with acute myeloid leukaemia (AML) or myelodysplasia (MDS)) or allogeneic (donor)-T-cells stimulated by DCleu, gain an efficient lysis of naive blasts, although not in every case. CXCL8, -9, -10, CCL2, -5 and Interleukin (IL-12) were quantified by Cytometric Bead Array (CBA) in supernatants from 5 DC-generating methods and correlated with AML-/MDS-patients’ serum-values, DC-/T-cell-interactions/antileukemic T-cell-reactions after mixed lymphocyte culture (MLC) and patients’ clinical course. The blast-lytic activity of T-cells stimulated with DC or mononuclear cells (MNC) was quantified in a cytotoxicity assay. Despite great variations of chemokine-levels, correlations with post-stimulation (after stimulating T-cells with DC in MLC) improved antileukemic T-cell activity were seen: higher released chemokine-values correlated with improved T-cells’ antileukemic activity (compared to stimulation with blast-containing MNC) - whereas with respect to the corresponding serum values higher CXCL8-, -9-, and -10- but lower CCL5- and -2-release correlated with improved antileukemic activity of DC-stimulated (vs. blast-stimulated) T-cells. In DC-culture supernatants higher chemokine-values correlated with post-stimulation improved antileukemic T-cell reactivity, whereas higher serum-values of CXCL8, -9, and -10 but lower serum-values of CCL5 and -2 correlated with post-stimulation improved antileukemic T-cell-reactivity. In a context of ‘DC’-stimulation (vs serum) this might point to a change of (CCL5 and -2-associated) functionality from a more ‘inflammatory’ or ‘tumor-promoting’ to a more ‘antitumor’-reactive functionality. This knowledge could contribute to develop immune-modifying strategies that promote antileukemic (adaptive) immune-responses.



中文翻译:

在“DC-培养基”中将 AML 母细胞转化为白血病衍生的树突状细胞 (DCleu) 改变了释放的趋化因子与抗白血病 T 细胞反应的相关性

树突状细胞 (DC) 和 T 细胞是 CTL 反应的介质。由 DC leu刺激的自体(来自急性髓性白血病 (AML) 或骨髓增生异常 (MDS) 患者)或同种异体(供体)-T 细胞可有效裂解幼稚原始细胞,但并非在所有情况下都如此。CXCL8、-9、-10、CCL2、-5 和白细胞介素 (IL-12) 通过流式细胞仪珠阵列 (CBA) 在来自 5 种 DC 生成方法的上清液中进行定量,并与 AML-/MDS-患者的血清相关值、混合淋巴细胞培养 (MLC) 和患者临床过程后的 DC-/T 细胞相互作用/抗白血病 T 细胞反应。在细胞毒性试验中量化了用 DC 或单核细胞 (MNC) 刺激的 T 细胞的裂解活性。尽管趋化因子水平变化很大,但与刺激后(在 MLC 中用 DC 刺激 T 细胞后)的相关性提高了抗白血病 T 细胞活性:较高的释放趋化因子值与提高的 T 细胞抗白血病活性相关(与用含有爆炸物的 MNC 刺激)——而相对于相应的血清值较高的 CXCL8-、-9- 和 -10- 但较低的 CCL5- 和 -2- 释放与 DC 刺激(相对于爆炸刺激) T 细胞的抗白血病活性改善相关。在 DC 培养上清液中,与刺激后相关的较高趋化因子值提高了抗白血病 T 细胞反应性,而较高的 CXCL8、-9 和 -10 血清值但较低的 CCL5 和 -2 血清值与刺激后相关改善抗白血病 T 细胞反应性。在“DC”刺激(相对于血清)的背景下,这可能表明(CCL5 和 -2 相关)功能从更“炎症”或“促肿瘤”变为更“抗肿瘤”反应性功能. 这些知识可能有助于开发促进抗白血病(适应性)免疫反应的免疫调节策略。

更新日期:2021-04-08
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