Myeloid cells expressing high level of CD45 are associated with a distinct activated phenotype in glioma
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ORIGINAL ARTICLE
Myeloid cells expressing high level of CD45 are associated with a distinct activated phenotype in glioma Susan Brandenburg 1 & Kati Turkowski 1 & Annett Mueller 1 & Yordan T. Radev 1 & Sabine Seidlitz 1 & Peter Vajkoczy 1,2
# Springer Science+Business Media New York 2017
Abstract 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 CD11b+CD45low and CD11b+CD45high. 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 CD11b+CD45high and the CD11b+CD45low cells. First, the majority of CD11b+CD45high cells expressed high level of GR1 and around 6% of IL10 representing in part features of myeloid-derived suppressor cells, while the CD11b+CD45low fraction displayed no upregulation of these molecules. Second, we detected that specifically the CD11b+CD45high 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
* Peter Vajkoczy [email protected] 1
Department of Experimental Neurosurgery, Charité – Universitätsmedizin Berlin, Berlin, Germany
2
Department of Neurosurgery, Charité – Universitätsmedizin Berlin, Berlin, Germany
CD11b+CD45low cell fraction, merely MHCII and TNFα were marginally overexpressed. In summary, these data emphasize the specific phenotype of CD11b+CD45high cells in glioma with suppressive as well as pro-inflammatory characteristics whereas the CD11b+CD45low cells were almost unaffected. Hence, primarily, the subpopulation consisting of CD45high-expressing cells is activated by the tumor and should be considered as therapeutic target. Keywords Microglia/macrophages . CD11b+CD45+ . Brain tumor . GR1 . MDSC
Introduction Glioblastoma multiforme (GBM) is one of the most aggressive types of malignant gliomas. This cancer is characterized by a high proliferative activity, a strong invasiveness, and an abnormal vasculature [1, 2]. A special feature of GBM is the high infiltration rate of myeloid cells whereby the resident immune cells of the central nervous system (CNS), microglia, and peripheral macrophages are part of the tumor tissue [3–6]. Analyses of rodent gliomas revealed two distinct myeloid cell populations, distinguished by their CD45 expression level. Previously, CD11b+CD45low
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