Tumor-Associated Myeloid Cell Dynamics in Glioma Microenvironments

Glioma microenvironments are densely populated by tumour-associated myeloid cells, comprising resident microglia and infiltrating macrophages. These cells exhibit remarkable phenotypic plasticity, often skewing towards an immunosuppressive, or “M2-like,” state that fosters tumour growth, angiogenesis and invasion. Hypoxic regions and glioma-derived cytokines such as colony-stimulating factor 1 (CSF-1), transforming growth factor-β and interleukin-6 (IL-6) drive alternative activation marked by elevated arginase-1, CD163 and secretion of anti-inflammatory mediators. Under danger signals or targeted interventions, myeloid cells can revert to a proinflammatory, “M1-like” phenotype, releasing nitric oxide, tumour necrosis factor-α and interleukin-1β that promote tumour cell death. Single-cell transcriptomics and spatial profiling have further revealed discrete myeloid subsets defined by unique metabolic programmes and surface markers, underscoring spatiotemporal heterogeneity. Deciphering the molecular circuits that sustain immunosuppression or enable reprogramming towards anti-tumour activity is essential for the development of next-generation glioma therapies.

Research from Nature Portfolio

Recent studies have illuminated how vascular niches sculpt myeloid behaviour in glioblastoma. Work has shown that endothelial-derived IL-6 and CSF-1 cooperatively induce arginase-1 expression and alternative macrophage activation via PPARγ-dependent transcriptional control of HIF-2α. Genetic ablation of IL-6 in endothelial cells attenuated immunosuppressive macrophage phenotypes, reduced tumour burden and extended survival in murine glioma models. These findings highlight the potential of disrupting angiocrine signals to rewire the glioma microenvironment and restore anti-tumour immunity.

Tumor-Associated Myeloid Cell Dynamics in Glioma Microenvironments publication trend

The graph below shows the total number of articles in tumor-associated myeloid cell dynamics in glioma microenvironments across all publications each year (not limited to Nature Index journals).

Technical terms

Tumour-Associated Myeloid Cells: Myeloid lineage immune cells, including microglia and macrophages, that infiltrate gliomas and modulate tumour progression.

Microglia: Resident immune cells of the central nervous system responsible for surveillance, phagocytosis and cytokine production.

Macrophage Polarisation: The process by which macrophages adopt distinct functional states, notably proinflammatory (M1) or anti-inflammatory (M2) phenotypes.

Angiocrine: Paracrine signals produced by endothelial cells that influence neighbouring cell behaviour within the vascular niche.

Hypoxia-Inducible Factor-2α (HIF-2α): A transcription factor activated under low oxygen conditions that regulates genes involved in angiogenesis and metabolic adaptation.

Exosomes: Nano-sized extracellular vesicles that carry proteins, lipids and nucleic acids to mediate intercellular communication.

References

1. Exosome-based nanoimmunotherapy targeting TAMs, a promising strategy for glioma. Cell Death & Disease (2023).
2. Knockdown of trem2 promotes proinflammatory microglia and inhibits glioma progression via the JAK2/STAT3 and NF-κB pathways. Cell Communication and Signaling (2024).
3. Tumor-associated macrophage-related strategies for glioma immunotherapy. npj Precision Oncology (2023).
4. When Immune Cells Turn Bad—Tumor-Associated Microglia/Macrophages in Glioma. International Journal of Molecular Sciences (2018).
5. Vascular niche IL-6 induces alternative macrophage activation in glioblastoma through HIF-2α. Nature Communications (2018).