分析 DLBCL 细胞和 EBV 转化 B 细胞产生的小细胞外囊泡 (sEV) 上的 CD20 和 PD-L1 水平,以及在 T 细胞抑制中的潜在作用。

IF 9.4 1区 医学 Q1 HEMATOLOGY
Hussein Akil, Hafidha Bentayeb, Marine Aitamer, Chantal Vignoles, Julie Abraham, Nathalie Gachard, Agnès Olivrie, Anne Guyot, Jessica Gobbo, Jean Feuillard, Hamasseh Shirvani, Danielle Troutaud
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引用次数: 0

摘要

越来越多的证据支持小细胞外囊泡(sEV,包括外泌体)在弥漫大B细胞淋巴瘤(DLBCL)的进展和治疗耐药性中发挥作用。CD20和PD-L1存在于DLBCL衍生的sEV上,但人们对其在患者层面的异质性知之甚少。此外,PD-L1+ sEV调节T细胞的能力也有待明确。在这里,我们分析了由人类 DLBCL 细胞系和 EBV 转化的 B 细胞-淋巴母细胞系(LCLs)产生的 sEV,这是一种允许自体 T 细胞共培养的模型。我们测定了患者样本与健康志愿者(HV)血浆 sEV 上的 CD20 和 PD-L1 水平,还研究了 sEV 在 CD4+ 和 CD8+ T 细胞上的功能相关性。LCL衍生的sEV上PD-L1的高表达与CD4+和CD8+T细胞的高凋亡率有关。患者血浆中的 sEV 浓度高于 HV。患者的 sEV-CD20 水平似乎更高,相比之下,sEV 中的 PD-L1 水平与 HV 中的 PD-L1 水平并无差异。患者和 HV 血浆样本中的 sEV 均显示出较高的糖基化 PD-L1 水平,这与对活化 T 细胞的相同抑制作用有关。我们的结论是,来自 EBV 转化 B 细胞的 sEV 具有免疫抑制作用,这种作用涉及细胞-细胞相互作用,可能至少涉及 PD-L1。此外,我们的研究结果表明,循环中的 sEV 有可能成为 DLBCL 的生物标志物来源,尤其是获得亲代肿瘤细胞免疫治疗靶标水平的信息。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Analysis of CD20 and PD-L1 levels on small extracellular vesicles (sEV) produced by DLBCL cells and EBV-transformed B cells, and potential role in T cell inhibition.

Increasing evidence supports a role for small extracellular vesicles (sEV, including exosomes) in Diffuse Large B-cell lymphoma (DLBCL) progression and resistance to treatment. CD20 and PD-L1 are found on DLBCL-derived sEV, but little is known about their patient-level heterogeneity. Moreover, the capacity of PD-L1+ sEV to modulate T cells needs to be clarified. Herein we analyzed sEV produced by human DLBCL cell lines and EBV-transformed B cell-lymphoblastoid cell lines (LCLs), a model allowing autologous T cell co-cultures. We determined CD20 and PD-L1 levels on plasma sEV from patient samples vs healthy volunteers (HV). sEV functional relevance was also investigated on CD4+ and CD8+ T cells. sEV derived from all cell lines showed an enrichment of CD20 and a high glycosylated PD-L1 expression when compared to cell lysates. High PD-L1 expression on LCL-derived sEV was associated with higher CD4+ and CD8+ T cell apoptosis. In patients, plasma sEV concentration was higher vs HV. Compared to sEV-CD20 level that seemed higher in patients, PD-L1 level in sEV was not different from those of HV. A high glycosylated PD-L1 level was shown in sEV from both patients and HV plasma samples, that was associated with the same inhibiting effect on activated T cells. We conclude that sEV derived from EBV-transformed B cells realize an immunosuppressive role that involved cell-cell interaction and probably at least PD-L1. Furthermore, our findings suggest the potential of circulating sEV as a source of biomarkers in DLBCL, notably to have information on immunotherapeutic target levels of parental tumor cells.

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来源期刊
CiteScore
12.60
自引率
7.30%
发文量
97
审稿时长
6 weeks
期刊介绍: Experimental Hematology & Oncology is an open access journal that encompasses all aspects of hematology and oncology with an emphasis on preclinical, basic, patient-oriented and translational research. The journal acts as an international platform for sharing laboratory findings in these areas and makes a deliberate effort to publish clinical trials with 'negative' results and basic science studies with provocative findings. Experimental Hematology & Oncology publishes original work, hypothesis, commentaries and timely reviews. With open access and rapid turnaround time from submission to publication, the journal strives to be a hub for disseminating new knowledge and discussing controversial topics for both basic scientists and busy clinicians in the closely related fields of hematology and oncology.
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