Brandenburg Susan, Turkowski Kati, Mueller Annett, Radev Yordan T, Seidlitz Sabine, Vajkoczy Peter
Department of Experimental Neurosurgery, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Immunol Res. 2017 Jun;65(3):757-768. doi: 10.1007/s12026-017-8915-1.
Glioblastoma multiforme is characterized by high accumulation of microglia/macrophages. The function of these tumor-infiltrating myeloid cells is not sufficiently elucidated. Therefore, a better understanding of the precise immune cell composition and function in brain tumors is required. In rodent glioma models, two different myeloid cell populations exist, determined by the expression level of CD45, namely CD11bCD45 and CD11bCD45. Previous analyses of cytokine and marker expression profiles were almost exclusively performed on the entire myeloid cell fraction. Consequently, described pro- and anti-tumoral characteristics were not assigned to the evident subpopulations. In the present study, we used a syngeneic glioblastoma mouse model and subsequent flow cytometric analyses to demonstrate the distinct properties of CD11bCD45 and the CD11bCD45 cells. First, the majority of CD11bCD45 cells expressed high level of GR1 and around 6% of IL10 representing in part features of myeloid-derived suppressor cells, while the CD11bCD45 fraction displayed no upregulation of these molecules. Second, we detected that specifically the CD11bCD45 population showed antigen-presenting, co-stimulatory, and inflammatory features. Here, we identified up to 80% of MHCII and approximately 50% of CD86 and TNFα-expressing cells. Investigation of MHCI and CD80 revealed a moderate upregulation. By contrast, in the CD11bCD45 cell fraction, merely MHCII and TNFα were marginally overexpressed. In summary, these data emphasize the specific phenotype of CD11bCD45 cells in glioma with suppressive as well as pro-inflammatory characteristics whereas the CD11bCD45 cells were almost unaffected. Hence, primarily, the subpopulation consisting of CD45-expressing cells is activated by the tumor and should be considered as therapeutic target.
多形性胶质母细胞瘤的特征是小胶质细胞/巨噬细胞高度聚集。这些肿瘤浸润性髓样细胞的功能尚未得到充分阐明。因此，需要更好地了解脑肿瘤中精确的免疫细胞组成和功能。在啮齿动物胶质瘤模型中，存在两种不同的髓样细胞群体，由CD45的表达水平决定，即CD11b⁺CD45⁻和CD11b⁺CD45⁺。先前对细胞因子和标志物表达谱的分析几乎完全是在整个髓样细胞部分进行的。因此，所描述的促肿瘤和抗肿瘤特征并未归因于明显的亚群。在本研究中，我们使用了同基因胶质母细胞瘤小鼠模型及随后的流式细胞术分析来证明CD11b⁺CD45⁻和CD11b⁺CD45⁺细胞的不同特性。首先，大多数CD11b⁺CD45⁻细胞表达高水平的GR1，约6%表达IL10，部分代表髓系来源抑制细胞的特征，而CD11b⁺CD45⁺部分未显示这些分子的上调。其次，我们检测到特别是CD11b⁺CD45⁺群体表现出抗原呈递、共刺激和炎症特征。在这里，我们鉴定出高达80%的MHCII以及约50%表达CD86和TNFα的细胞。对MHCI和CD80的研究显示有适度上调。相比之下，在CD11b⁺CD45⁻细胞部分，仅MHCII和TNFα有轻微过表达。总之，这些数据强调了胶质瘤中CD11b⁺CD45⁻细胞具有抑制和促炎特征的特定表型，而CD11b⁺CD45⁺细胞几乎未受影响。因此，主要由表达CD45的细胞组成的亚群被肿瘤激活，应被视为治疗靶点。
