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Regulation of Microglia for the Treatment of Glioma
1Department of Neurosurgery, NewYork-Presbyterian/Weill Cornell Medicine, New York, New York, USA.
Abstract:
Microglia are the resident macrophages of the central nervous system (CNS). They are derived from the erythromyeloid progenitors in the embryonic yolk sac, and they are maintained postnatally by limited self-renewal and longevity. As the most abundant immune cells in the CNS, they play critical roles in homeostasis and various CNS pathologies, including tumor, stroke, and neurodegenerative disease. For instance, in gliomas, up to more than 30% of cells in the tumor microenvironment can be microglia and tumor-associated macrophages. These cells are typically coopted by tumor cells to create a pro-tumorigenic microenvironment. The transcriptional regulation of the development and function of microglia in health and disease is not well understood. Transcription factors are master regulators of cell fates and functions and activate target genes that execute a genetic program typically initiated by external stimuli. Several transcription factors, not necessarily specific to microglia, have been shown to play roles in the development, function, and activation state of microglia. In this review, we summarize our current understanding of the roles of transcription factors in the functions of microglia in normal CNS homeostasis and in gliomas. A thorough understanding of the transcription factors and their target genes that mediate and regulate the functions of microglia in gliomas may help identify new targets for immune therapies. These stroma-directed therapies may be combined with tumor cell-directed therapies for more effective treatment of these diseases.
Insights
Microglia, the CNS immune cells, are key in brain health and disease. Understanding transcription factors controlling microglia in gliomas can reveal new therapeutic targets for brain tumors.
Area of Science:
- Neuroimmunology
- Molecular Biology
- Oncology
Background:
- Microglia are the primary immune cells of the central nervous system (CNS), originating from embryonic erythromyeloid progenitors.
- These cells are crucial for CNS homeostasis and implicated in various pathologies, including tumors, stroke, and neurodegenerative diseases.
- In gliomas, microglia and tumor-associated macrophages can constitute over 30% of the tumor microenvironment, often promoting tumor growth.
Purpose of the Study:
- To review the current understanding of transcription factors regulating microglial development and function in the CNS.
- To specifically examine the roles of transcription factors in microglial functions within the context of glioma microenvironments.
- To highlight the potential of targeting transcription factors for novel immunotherapies against gliomas.
Main Methods:
- Literature review summarizing existing research on transcription factors and microglia.
- Analysis of the known roles of transcription factors in microglial biology, both in normal CNS function and in disease states.
- Focus on transcription factors influencing microglia within the tumor microenvironment, particularly in gliomas.
Main Results:
- Transcription factors are critical regulators of microglial cell fate, function, and activation states.
- Several transcription factors, not exclusive to microglia, influence their development and activity.
- In gliomas, microglia are co-opted by tumor cells, and their functions are transcriptionally regulated, contributing to a pro-tumorigenic environment.
Conclusions:
- A comprehensive understanding of transcription factors governing microglia in gliomas is essential.
- Identifying specific transcription factors and their targets in glioma-associated microglia can reveal novel therapeutic avenues.
- Targeting these transcription factors offers potential for developing stroma-directed therapies, possibly in combination with existing treatments, for improved glioma management.
