Microglia and brain macrophages are differentially associated with tumor necrosis in glioblastoma: A link to tumor progression.

Background: Microglia and brain macrophages contribute significantly to the tumor microenvironment in highly malignant glioblastoma where they are considered important drivers of tumor progression. A better understanding of the role of the brain macrophages present in glioblastoma appears crucial for improving therapeutic outcomes, especially in the context of novel immunotherapeutic approaches. Methods: We investigated the regulation of two well-established markers for microglia and brain macrophages, IBA1 and CD163, in relation to glioblastoma tumor necrosis using immunohistochemistry and modality fusion heatmaps of whole slide images obtained from adjacent tissue sections. Results: IBA1 and CD163 showed remarkable differences in relation to glioblastoma tumor necrosis. Generally, IBA1 immunoreactive cells were far less common in necrotic tissue areas than CD163-expressing cells. We also found extensive and frequently diffuse extracellular CD163 deposition, especially in hypocellular necrobiotic tumor regions where IBA1 was typically absent. Conclusions: Resident microglia seem more likely to be important for the diffuse infiltration of glioma cells in hypercellular tissue areas, whereas myeloid macrophages may be the main macrophage population in the wake of tumor necrosis. Since the necrotic niche with its interactions between microglia, brain macrophages, and glioblastoma/glioma stem cells is increasingly recognised as an important factor in tumor progression, further detailed studies of the macrophage populations in glioblastoma are warranted.