Department of Experimental and Clinical Medicine, "Magna Graecia" University and Medical Oncology Unit, T. Campanella Cancer Center, "Salvatore Venuta" University Campus , Catanzaro , Italy.
Unit of Radiotherapy, Siena University Hospital , Siena , Italy.
Front Oncol. 2014 Dec 8;4:348. doi: 10.3389/fonc.2014.00348. eCollection 2014.
Immunosuppressive cells have been reported to play an important role in tumor-progression mainly because of their capability to promote immune-escape, angiogenesis, and metastasis. Among them, myeloid-derived suppressor cells (MDSCs) have been recently identified as immature myeloid cells, induced by tumor-associated inflammation, able to impair both innate and adaptive immunity. While murine MDSCs are usually identified by the expression of CD11b and Gr1, human MDSCs represent a more heterogeneous population characterized by the expression of CD33 and CD11b, low or no HLA-DR, and variable CD14 and CD15. In particular, the last two may alternatively identify monocyte-like or granulocyte-like MDSC subsets with different immunosuppressive properties. Recently, a substantial increase of MDSCs has been found in peripheral blood and bone marrow (BM) of multiple myeloma (MM) patients with a role in disease progression and/or drug resistance. Pre-clinical models recapitulating the complexity of the MM-related BM microenvironment (BMM) are major tools for the study of the interactions between MM cells and cells of the BMM (including MDSCs) and for the development of new agents targeting MM-associated immune-suppressive cells. This review will focus on current strategies for human MDSCs generation and investigation of their immunosuppressive function in vitro and in vivo, taking into account the relevant relationship occurring within the MM-BMM. We will then provide trends in MDSC-associated research and suggest potential application for the treatment of MM.
免疫抑制细胞在肿瘤进展中发挥重要作用，主要是因为它们能够促进免疫逃逸、血管生成和转移。其中，髓源性抑制细胞（MDSCs）最近被鉴定为肿瘤相关炎症诱导的未成熟髓系细胞，能够损害固有和适应性免疫。虽然鼠 MDSCs 通常通过 CD11b 和 Gr1 的表达来识别，但人 MDSCs 是一种更具异质性的群体，其特征是 CD33 和 CD11b 的表达、低或无 HLA-DR，以及可变的 CD14 和 CD15。特别是，后两者可能替代地识别具有不同免疫抑制特性的单核细胞样或粒细胞样 MDSC 亚群。最近，多发性骨髓瘤（MM）患者的外周血和骨髓（BM）中发现 MDSCs 大量增加，其在疾病进展和/或耐药性中发挥作用。模拟 MM 相关 BM 微环境（BMM）复杂性的临床前模型是研究 MM 细胞与 BMM 细胞（包括 MDSCs）之间相互作用以及开发针对 MM 相关免疫抑制细胞的新药物的主要工具。这篇综述将重点介绍目前在体外和体内生成人 MDSCs 并研究其免疫抑制功能的策略，同时考虑到 MM-BMM 中发生的相关关系。然后，我们将提供 MDSC 相关研究的趋势，并提出潜在的 MM 治疗应用。
