Bizymi Nikoleta, Bjelica Sunčica, Kittang Astrid Olsnes, Mojsilovic Slavko, Velegraki Maria, Pontikoglou Charalampos, Roussel Mikael, Ersvær Elisabeth, Santibañez Juan Francisco, Lipoldová Marie, Papadaki Helen A
Hemopoiesis Research Laboratory, School of Medicine, University of Crete and Department of Hematology, University Hospital of Heraklion, Heraklion, Greece.
Graduate Program Molecular Basis of Human Disease, School of Medicine, University of Crete, Heraklion, Greece.
Hemasphere. 2019 Jan 28;3(1):e168. doi: 10.1097/HS9.0000000000000168. eCollection 2019 Feb.
Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immature myeloid cells that exist at very low numbers in healthy subjects but can expand significantly in malignant, infectious, and chronic inflammatory diseases. These cells are characterized as early-MDSCs, monocytic-MDSCs, and polymorphonuclear-MDSCs and can be studied on the basis of their immunophenotypic characteristics and their functional properties to suppress T-cell activation and proliferation. MDSCs have emerged as important contributors to tumor expansion and chronic inflammation progression by inducing immunosuppressive mechanisms, angiogenesis and drug resistance. Most experimental and clinical studies concerning MDSCs have been mainly focused on solid tumors. In recent years, however, the implication of MDSCs in the immune dysregulation associated with hematologic malignancies, immune-mediated cytopenias and allogeneic hemopoietic stem cell transplantation has been documented and the potential role of these cells as biomarkers and therapeutic targets has started to attract a particular interest in hematology. The elucidation of the molecular and signaling pathways associated with the generation, expansion and function of MDSCs in malignant and immune-mediated hematologic diseases and the clarification of mechanisms related to the circulation and the crosstalk of MDSCs with malignant cells and other components of the immune system are anticipated to lead to novel therapeutic strategies. This review summarizes all available evidence on the implication of MDSCs in hematologic diseases highlighting the challenges and perspectives arising from this novel field of research.
髓源性抑制细胞(MDSC)是一组异质性的未成熟髓样细胞,在健康受试者中数量极少,但在恶性肿瘤、感染性疾病和慢性炎症性疾病中可显著扩增。这些细胞可分为早期MDSC、单核细胞样MDSC和多形核MDSC,可根据其免疫表型特征和抑制T细胞活化与增殖的功能特性进行研究。MDSC通过诱导免疫抑制机制、血管生成和耐药性,已成为肿瘤进展和慢性炎症发展的重要促成因素。大多数关于MDSC的实验和临床研究主要集中在实体瘤上。然而,近年来,已有文献记载MDSC在与血液系统恶性肿瘤、免疫介导的血细胞减少症和异基因造血干细胞移植相关的免疫失调中的作用,并且这些细胞作为生物标志物和治疗靶点的潜在作用已开始在血液学领域引起特别关注。阐明与恶性和免疫介导的血液系统疾病中MDSC的产生、扩增和功能相关的分子和信号通路,以及阐明与MDSC的循环及其与恶性细胞和免疫系统其他成分的相互作用相关的机制,有望带来新的治疗策略。本综述总结了关于MDSC在血液系统疾病中的作用的所有现有证据,突出了这一新兴研究领域所带来的挑战和前景。