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Published on: October 20, 2016
Immune biology of glioma-associated macrophages and microglia: functional and therapeutic implications
Jun Wei1, Peiwen Chen2, Pravesh Gupta3
1Departments of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Abstract:
CNS immune defenses are marshaled and dominated by brain resident macrophages and microglia, which are the innate immune sentinels and frontline host immune barriers against various pathogenic insults. These myeloid lineage cells are the predominant immune population in gliomas and can constitute up to 30-50% of the total cellular composition. Parenchymal microglial cells and recruited monocyte-derived macrophages from the periphery exhibit disease-specific phenotypic characteristics with spatial and temporal distinctions and are heterogeneous subpopulations based on their molecular signatures. A preponderance of myeloid over lymphoid lineage cells during CNS inflammation, including gliomas, is a contrasting feature of brain immunity relative to peripheral immunity. Herein we discuss glioma-associated macrophage and microglia immune biology in the context of their identity, molecular drivers of recruitment, nomenclature and functional paradoxes, therapeutic reprogramming and polarization strategies, relevant challenges, and our perspectives on therapeutic modulation.
Insights
Brain-resident microglia and infiltrating macrophages are key immune cells in gliomas, presenting unique characteristics and therapeutic targets. Understanding their biology is crucial for developing effective brain cancer immunotherapies.
Area of Science:
- Neuroimmunology
- Oncology
- Immunology
Background:
- Central nervous system (CNS) immunity relies on microglia and macrophages as primary defenders against pathogens.
- In gliomas, these myeloid cells are abundant, comprising up to 50% of tumor composition.
- Brain immunity differs from peripheral immunity, with a dominance of myeloid over lymphoid cells during inflammation.
Purpose of the Study:
- To explore the immune biology of glioma-associated macrophages and microglia.
- To discuss their identity, recruitment, nomenclature, and functional roles.
- To review therapeutic reprogramming strategies and challenges in glioma treatment.
Main Methods:
- Review of current literature on glioma-associated myeloid cells.
- Analysis of molecular signatures and phenotypic heterogeneity.
- Discussion of therapeutic modulation approaches.
Main Results:
- Glioma-associated myeloid cells exhibit distinct spatial and temporal characteristics.
- These cells are heterogeneous subpopulations with unique molecular signatures.
- Myeloid cell preponderance is a hallmark of brain immunity in gliomas.
Conclusions:
- Targeting glioma-associated macrophages and microglia offers a promising therapeutic avenue.
- Understanding their complex biology is essential for effective immunomodulation strategies.
- Further research is needed to overcome challenges in therapeutic reprogramming.
