Journal
EUROPEAN JOURNAL OF IMMUNOLOGY
Volume 53, Issue 4, Pages -Publisher
WILEY
DOI: 10.1002/eji.202250161
Keywords
glioma; tumor microenvironment; microglia; monocyte-derived macrophages
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Gliomas, the most common primary brain tumors, are influenced by the tumor microenvironment comprised of tumor-associated microglia (TA-MG) and monocyte-derived macrophages (MDM). This study reveals the distinct spatial and temporal differences between TA-MG and MDM during glioma progression. TA-MG are found both inside and outside the tumor but are eliminated as the tumor progresses, while MDM are only present inside the tumor. Additionally, the study shows that TA-MG and MDM exhibit different enrichment in the perivascular area. These findings highlight the unique roles of TA-MG and MDM in glioma progression.
Gliomas are the most frequent primary tumors of the brain. Glioma progression is regulated by the tumor microenvironment, which is mainly composed 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 MDMs differ in their spatiotemporal distribution and interaction with other components of the glioma microenvironment. MDM were present only inside the tumor, whereas TA-MG accumulated both outside and inside the tumor. However, TA-MG was eliminated from the tumor mass as the tumor progressed. Depletion of MDM led to enhanced occupancy of TA-MG in the tumor core, indicating that TA-MG elimination was regulated by MDM. TA-MG and MDM are heterogeneous cell populations whose compositions and properties can change during tumor progression. Finally, MG, TA-MG and MDM were enriched in the perivascular area (PVA) compared to more distal blood vessel-associated areas. However, inside the tumor, the MDM enrichment in PVA was higher than that in TA-MG. Collectively, we established that TA-MG and MDM exhibit different spatiotemporal features in glioma, suggesting distinctive roles during tumor progression.
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