Gielen Paul R, Schulte Barbara M, Kers-Rebel Esther D, Verrijp Kiek, Petersen-Baltussen Harriëtte M J M, ter Laan Mark, Wesseling Pieter, Adema Gosse J
From the Tumor Immunology Laboratory, Radboud Institute for Molecular Life Sciences (PRG, BMS, EDK-R, GJA); and Departments of Pathology (KV, PW) and Neurosurgery (HMJMP-B, ML), Radboud University Medical Center, Nijmegen; and Department of Pathology, VU University Medical Center, Amsterdam (PW), the Netherlands.
J Neuropathol Exp Neurol. 2015 May;74(5):390-400. doi: 10.1097/NEN.0000000000000183.
Myeloid-derived suppressor cells (MDSCs), defined as CD33-positive major histocompatibility complex class II-negative cells, are increased in a variety of human tumors and are associated with immunosuppression. Myeloid-derived suppressor cells can be further subdivided into CD14-positive monocytic MDSC and CD15-positive granulocytic MDSC (polymorphonuclear MDSC) subpopulations. Here we analyzed MDSC subsets in the blood and tumor tissue of patients with glioma, including the most malignant variant, glioblastoma multiforme (GBM). CD33-positive major histocompatibility complex class II-negative MDSCs in blood from 21 patients with glioma and 12 healthy individuals were phenotyped and quantified by flow cytometry. Myeloid populations of the monocytic MDSC and polymorphonuclear MDSC phenotypes were both significantly increased in the blood of patients with GBM versus healthy controls. The myeloid activation markers CD80 and PD-L1 could not be detected on either of these MDSC subsets; CD124, CD86, and CD40 were detected at similar levels on MDSCs in patients with glioma and healthy donors. By contrast, in tumor cell suspensions, the MDSC population consisted almost exclusively of CD15-positive cells. Immunohistochemistry confirmed infiltration of CD15-positive major histocompatibility complex class II-negative cells in glioma tissue samples. These data support a role for cells with an MDSC phenotype in the blood and tumor microenvironment of patients with GBM.
髓系来源的抑制性细胞（MDSCs）被定义为CD33阳性、主要组织相容性复合体II类阴性的细胞，在多种人类肿瘤中数量增加，并与免疫抑制相关。髓系来源的抑制性细胞可进一步细分为CD14阳性的单核细胞型MDSC和CD15阳性的粒细胞型MDSC（多形核MDSC）亚群。在此，我们分析了胶质瘤患者血液和肿瘤组织中的MDSC亚群，包括最恶性的变体多形性胶质母细胞瘤（GBM）。通过流式细胞术对21例胶质瘤患者和12名健康个体血液中的CD33阳性、主要组织相容性复合体II类阴性MDSCs进行表型分析和定量。与健康对照相比，GBM患者血液中的单核细胞型MDSC和多形核MDSC表型的髓系细胞群均显著增加。在这两种MDSC亚群中均未检测到髓系激活标志物CD80和PD-L1；在胶质瘤患者和健康供体的MDSCs上，CD124、CD86和CD40的检测水平相似。相比之下，在肿瘤细胞悬液中，MDSC群体几乎完全由CD15阳性细胞组成。免疫组织化学证实了CD15阳性、主要组织相容性复合体II类阴性细胞在胶质瘤组织样本中的浸润。这些数据支持具有MDSC表型的细胞在GBM患者血液和肿瘤微环境中的作用。
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