Differences in myeloid cell subfractions in human GBM microenvironment determine alternate proangiogenic phenotype
Anne Blank, Charité - Universitätsmedizin Berlin, Department of Neurosurgery; Susan Brandenburg, Charité - Universitätsmedizin Berlin, Department of Neurosurgery; Ulf Schneider, Charité - Universitätsmedizin Berlin, Department of Neurosurgery; Peter Vajkoczy, Charité - Universitätsmedizin Berlin, Department of Neurosurgery
Recently, GBM research focused on interactions of tumor cells and their microenvironment, for instance immune and endothelial cells. We therefore aimed to explore the contribution of immune cells from the myeloid lineage to glioma vascularization and progression.
Thus, we collected tissue samples of 65 patients suffering from GBM, astrocytoma WHO °III or epilepsy (control) and used FACS analyses and immunofluorescence stainings to investigate the phenotype of the myeloid cell fraction. In addition, isolation of CD11b+ cells was performed and these cells were used for RNA purification followed by RT-PCR to detect proangiogenic molecules.
We defined subgroups of GBM patients by the percentage of infiltrated granulocytes. Here, one group showed low levels of granulocytes while the other contained up to 50% of granulocytes within the myeloid cell fraction. In the last mentioned patients the expression of various proangiogenic factors was highly upregulated. Additionally, a remodeling of the glioma vasculature and an increased association of myeloid cells with tumor blood vessels could be observed. In general, the microglia/macrophages in GBM tissue revealed an activation status that was distinct from astrocytoma WHO °III, whereby antigen-presenting molecules and co-stimulatory factors were overexpressed.
These data support the importance of myeloid cells for tumor vascularization and progression and represent a therapeutic target to improve the median survival of GBM patients.