Myeloid cells expressing high level of CD45 are associated with a distinct activated phenotype in glioma.

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.