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The MHC-II antigen presentation machinery and B7 checkpoint ligands display distinctive patterns correlated with acute myeloid leukaemias blast cells HLA-DR expression
Immunobiology ( IF 2.8 ) Pub Date : 2020-12-03 , DOI: 10.1016/j.imbio.2020.152049
Ion Antohe 1 , Mariana Pavel Tanasa 2 , Angela Dăscălescu 1 , Cătălin Dănăilă 1 , Amalia Titieanu 1 , Mihaela Zlei 3 , Iuliu Ivanov 4 , Adriana Sireteanu 4 , Petru Cianga 2
Affiliation  

Acute Myeloid Leukaemia (AML) is a neoplasia characterised by rapid proliferation and an increased rate of relapses. The AML blasts display features of antigen-presenting cells (APC), and thus can directly modulate the anti-tumour T cell responses. The bone marrow of a group consisting of 30 newly diagnosed patients and four healthy donors (HD) was investigated for the expression of HLA-DR, several molecules involved in MHC-II antigen-presentation and MHC-II groove editing, like HLA-DM, CD74 and CLIP, as well as a set of immune checkpoint ligands, like ICOS-L, B7.2, PD-L2 and B7-H3. The patients were further characterised for their genetic anomalies and distributed to favourable, intermediate and adverse ELN risk categories. We were able to show that while 23% of our patients displayed a low level of HLA-DR surface expression, all patients displayed higher HLA-DM and CD74 expression compared to HD. However, a higher CLIP expression was noticed only in the HLA-DR low patients. The co-inhibitory PD-L2 and B7-H3 molecules were increased in the cases with normal HLA-DR expression; oppositely, the co-stimulatory ICOS-L and the dual function B7.2 were significantly increased in the cases with HLA-DR low expression. Furthermore, no favourable ELN risk cases were found within the HLA-DR low group. All in all, these data show that the AML with low versus normal HLA-DR expression display different profiles of MHC class II machinery molecules and B7 ligands, which are correlated with distinct ELN stratification. Furthermore, as our study included healthy individuals, it offers valuable information about the expression levels that should be considered as normal for these markers known to cause differences in peptide repertoires, reflected further in distinct T-cells polarisation pathways.



中文翻译:

MHC-II 抗原呈递机制和 B7 检查点配体显示出与急性髓系白血病母细胞 HLA-DR 表达相关的独特模式

急性髓性白血病 (AML) 是一种以快速增殖和复发率增加为特征的肿瘤。AML 原始细胞显示抗原呈递细胞 (APC) 的特征,因此可以直接调节抗肿瘤 T 细胞反应。研究了由 30 名新诊断患者和 4 名健康供体 (HD) 组成的一组骨髓中 HLA-DR 的表达,这些分子涉及 MHC-II 抗原呈递和 MHC-II 凹槽编辑,如 HLA-DM 、CD74 和 CLIP,以及一组免疫检查点配体,如 ICOS-L、B7.2、PD-L2 和 B7-H3。这些患者的遗传异常进一步被表征,并被分为有利、中等和不利的 ELN 风险类别。我们能够证明,虽然 23% 的患者表现出低水平的 HLA-DR 表面表达,与 HD 相比,所有患者都表现出更高的 HLA-DM 和 CD74 表达。然而,仅在 HLA-DR 低的患者中发现了较高的 CLIP 表达。在 HLA-DR 表达正常的情况下,共抑制 PD-L2 和 B7-H3 分子增加;相反,在 HLA-DR 低表达的情况下,共刺激 ICOS-L 和双重功能 B7.2 显着增加。此外,在 HLA-DR 低组中未发现有利的 ELN 风险病例。总而言之,这些数据表明,2 在 HLA-DR 低表达的情况下显着增加。此外,在 HLA-DR 低组中未发现有利的 ELN 风险病例。总而言之,这些数据表明,2 在 HLA-DR 低表达的情况下显着增加。此外,在 HLA-DR 低组中未发现有利的 ELN 风险病例。总而言之,这些数据表明,正常的 HLA-DR 表达相比,显示出不同的 MHC II 类机械分子和 B7 配体,它们与不同的 ELN 分层相关。此外,由于我们的研究包括健康个体,它提供了有关表达水平的有价值信息,这些表达水平应该被认为是正常的,这些标记已知会导致肽库的差异,进一步反映在不同的 T 细胞极化途径中。

更新日期:2020-12-25
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