MRC Centre for Reproductive Health, The University of Edinburgh The Queen's Medical Research Institute, Edinburgh, Edinburgh, UK.
Department of Otorhinolaryngology, University Hospital Essen, Essen, Germany.
J Immunother Cancer. 2020 Sep;8(2). doi: 10.1136/jitc-2020-001223.
Myeloid-derived suppressor cells (MDSC) are a functional myeloid cell subset that includes myeloid cells with immune suppressive properties. The presence of MDSC has been reported in the peripheral blood of patients with several malignant and non-malignant diseases. So far, direct comparison of MDSC across different diseases and Centers is hindered by technical pitfalls and a lack of standardized methodology. To overcome this issue, we formed a network through the COST Action Mye-EUNITER (www.mye-euniter.eu) with the goal to standardize and facilitate the comparative analysis of human circulating MDSC in cancer, inflammation and infection. In this manuscript, we present the results of the multicenter study Mye-EUNITER MDSC Monitoring Initiative, that involved 13 laboratories and compared circulating MDSC subsets across multiple diseases, using a common protocol for the isolation, identification and characterization of these cells.
We developed, tested, executed and optimized a standard operating procedure for the isolation and immunophenotyping of MDSC using blood from healthy donors. We applied this procedure to the blood of almost 400 patients and controls with different solid tumors and non-malignant diseases. The latter included viral infections such as HIV and hepatitis B virus, but also psoriasis and cardiovascular disorders.
We observed that the frequency of MDSC in healthy donors varied substantially between centers and was influenced by technical aspects such as the anticoagulant and separation method used. Expansion of polymorphonuclear (PMN)-MDSC exceeded the expansion of monocytic MDSC (M-MDSC) in five out of six solid tumors. PMN-MDSC expansion was more pronounced in cancer compared with infection and inflammation. Programmed death-ligand 1 was primarily expressed in M-MDSC and e-MDSC and was not upregulated as a consequence of disease. LOX-1 expression was confined to PMN-MDSC.
This study provides improved technical protocols and workflows for the multi-center analysis of circulating human MDSC subsets. Application of these workflows revealed a predominant expansion of PMN-MDSC in solid tumors that exceeds expansion in chronic infection and inflammation.
髓系来源的抑制细胞（MDSC）是具有免疫抑制功能的功能性髓系细胞亚群。已经在几种恶性和非恶性疾病患者的外周血中报告了 MDSC 的存在。到目前为止，由于技术缺陷和缺乏标准化方法，不同疾病和中心之间的 MDSC 直接比较受到阻碍。为了克服这个问题，我们通过 COST 行动 Mye-EUNITER（www.mye-euniter.eu）建立了一个网络，目标是标准化和促进癌症、炎症和感染中人类循环 MDSC 的比较分析。在本文中，我们介绍了多中心研究 Mye-EUNITER MDSC 监测倡议的结果，该研究涉及 13 个实验室，使用分离、鉴定和表征这些细胞的通用方案比较了多种疾病中的循环 MDSC 亚群。
我们开发、测试、执行并优化了一种使用健康供体血液分离和免疫表型分析 MDSC 的标准操作程序。我们将该程序应用于近 400 名患有不同实体瘤和非恶性疾病的患者和对照者的血液中。后者包括艾滋病毒和乙型肝炎病毒等病毒感染，还包括银屑病和心血管疾病。
我们观察到，健康供体中 MDSC 的频率在中心之间有很大差异，并且受到技术方面的影响，如使用的抗凝剂和分离方法。在六种实体瘤中的五种中，多形核（PMN）-MDSC 的扩增超过单核 MDSC（M-MDSC）的扩增。与感染和炎症相比，癌症中 PMN-MDSC 的扩增更为明显。程序性死亡配体 1 主要在 M-MDSC 和 e-MDSC 中表达，并且不会因疾病而上调。LOX-1 表达仅限于 PMN-MDSC。
这项研究为循环人类 MDSC 亚群的多中心分析提供了改进的技术方案和工作流程。这些工作流程的应用显示，在实体瘤中，PMN-MDSC 的扩增明显超过慢性感染和炎症中的扩增。
