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Published on: July 31, 2017
Peritumoral Microenvironment in High-Grade Gliomas: From FLAIRectomy to Microglia-Glioma Cross-Talk
Roberto Altieri1,2, Davide Barbagallo2,3, Francesco Certo1,2
1Department of Neurological Surgery, Policlinico "G. Rodolico-S. Marco" University Hospital, 95121 Catania, Italy.
Abstract:
Cellular composition and molecular signatures of the glioma core compared with infiltrative margins are different, and it is well known that the tumor edge is enriched in microglia. In this review of the literature, we summarize the role of the peritumoral area in high-grade gliomas (HGGs) from surgical and biological points of view. There is evidence on the dual role of microglia in HGGs-a scavenger-tumoricidal role when microglia are activated in an M1 phenotype and a role favoring tumor growth and infiltration/migration when microglia are activated in an M2 phenotype. Microglia polarization is mediated by complex pathways involving cross-talk with glioma cells. In this scenario, extracellular vesicles and their miRNA cargo seem to play a central role. The switch to a specific phenotype correlates with prognosis and the pathological assessment of a specific microglial setting can predict a patient's outcome. Some authors have designed an engineered microglial cell as a biologically active vehicle for the delivery of intraoperative near-infrared fluorescent dye with the aim of helping surgeons detect peritumoral infiltrated areas during resection. Furthermore, the pharmacological modulation of microglia-glioma cross-talk paves the way to more effective therapies.
Insights
Microglia in high-grade gliomas (HGGs) have a dual role, either fighting or promoting tumor growth. Targeting microglia-glioma interactions offers new therapeutic strategies for HGGs.
Area of Science:
- Neuro-oncology
- Immunology
- Cancer Biology
Background:
- The peritumoral area in high-grade gliomas (HGGs) exhibits distinct cellular and molecular characteristics compared to the tumor core.
- Microglia, immune cells of the central nervous system, are notably abundant at the tumor margins in HGGs.
Purpose of the Study:
- To review the literature on the role of the peritumoral area in HGGs from both surgical and biological perspectives.
- To elucidate the dual function of microglia in HGG progression and their interaction with glioma cells.
Main Methods:
- Literature review focusing on the surgical and biological aspects of the peritumoral microenvironment in HGGs.
- Analysis of studies investigating microglia polarization (M1 vs. M2 phenotypes) and its implications in HGGs.
- Examination of the role of extracellular vesicles and microRNAs in microglia-glioma cross-talk.
Main Results:
- Microglia exhibit a dual role: M1 phenotype is tumoricidal, while M2 phenotype promotes tumor growth and infiltration.
- Microglia polarization is influenced by complex signaling pathways and cross-talk with glioma cells, with extracellular vesicles and miRNAs playing a key role.
- The specific microglial phenotype correlates with patient prognosis, and its pathological assessment can predict outcomes.
Conclusions:
- Understanding microglia polarization and their interaction with glioma cells is crucial for HGG management.
- Engineered microglia and pharmacological modulation of microglia-glioma cross-talk represent promising avenues for novel HGG therapies.
- Targeting the peritumoral microenvironment, particularly microglia, holds potential for improving surgical resection and therapeutic efficacy in HGGs.
