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

Kaveri Banerjee, Avinoam Ratzabi, Itai M Caspit, Or Ganon, Pablo Blinder, Steffen Jung, Reuven Stein

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Article numbere2250161
Number of pages45
JournalEuropean Journal of Immunology
Volume53
Issue number4
Early online date17 Jan 2023
DOIs
StatePublished - Apr 2023

Keywords

  • glioma
  • microglia
  • monocyte-derived macrophages
  • tumor microenvironment

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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