Distinct spatiotemporal features of microglia and monocyte-derived macrophages in glioma.

Gliomas are the most frequent primary tumors of the brain. Glioma progression is regulated by the tumor microenvironment, which is mainly comprised of tumor-associated microglia (TA-MG) and monocyte-derived macrophages (MDM). Recent studies have highlighted the distinct properties of these cells in glioma progression. However, their spatiotemporal alteration during tumor progression has not been fully explored. Using a genetic lineage tracing approach, we show that TA-MG and MDM differ in their spatiotemporal distribution and interaction with other components of the glioma microenvironment. MDM were present only inside the tumor, whereas TA-MG accumulate both outside and inside the tumor. However, TA-MG were eliminated from the tumor mass as the tumor progressed. Depletion of MDM, led to enhanced occupancy of TA-MG in the tumor core, indicating the TA-MG elimination was regulated by MDM. TA-MG and MDM are heterogeneous cell populations, whose compositions and properties can change during tumor progression. Lastly, MG, TA-MG and MDM were enriched in the perivascular area (PVA) compared to more distally blood vessel-associated areas. However, inside the tumor the MDM enrichment in the PVA was higher than that of TA-MG. Collectively, we establish that TA-MG and MDM exhibit different spatiotemporal features in glioma, suggesting distinctive role during tumor progression. This article is protected by copyright. All rights reserved.