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Exploiting Microglial Functions for the Treatment of Glioblastoma
Cinzia Dello Russo1, Lucia Lisi, Lucio Tentori
1Institute of Pharmacology, Catholic University Medical School, Rome, Italy.
Background:
Glioblastoma multiforme (GBM) is the most common brain tumor in adults and is associated with a very low survival rate. The heterogeneity of the tumor microenvironment, its resistance to drug and radiation therapy, and its robust invasiveness all contribute to the poor outcome. Large numbers of glioma associated microglia and macrophages (GAMs) can accumulate within the tumor where they appear to have an important role in prognosis.
Methods:
An extensive revision of current available literature on this topic has been carried out, using the PubMed database. Articles exploring the contribution of GAMs to GBM biology as well as evidence that GAMs can be pharmacologically modulated to inhibit tumor growth are critically discussed in this review article.
Results:
GAMs constitute the largest portion of tumor infiltrating cells contributing up to 30% of the entire glioma mass. Upon interaction with neoplastic cells, GAMs acquire a unique phenotype of activation including both M1 and M2 specific markers. Different profiles of activation usually co-exist in the same tumor that is dependent upon GAM location or stage of disease. In addition to regulating immune responses which may control or favor astrocyte malignant transformation, GAMs are directly involved in the degradation of the extracellular matrix (ECM), a crucial mechanism that allows the expansion of tumors and parenchyma invasion. Several pharmacological strategies have been developed which interfere with GAM recruitment at the tumor site, cell polarization and immune function, and ECM remodeling by GAM-secreted factors. The most promising therapeutic approaches appear to target both GBM cells and GAM biological properties.
Conclusion:
GAMs significantly contribute to GBM biology (favoring tumor growth and invasiveness). Data reviewed in the present article suggest that these cells represent a valuable alternative/ additional target for the development of more effective treatments for GBM.
Insights
Glioma-associated microglia and macrophages (GAMs) fuel glioblastoma growth and invasion. Targeting these cells alongside glioblastoma cells offers a promising therapeutic strategy for improving patient outcomes.
Area of Science:
- Neuro-oncology
- Cancer immunology
- Tumor microenvironment
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor prognosis.
- Tumor microenvironment, drug resistance, and invasiveness contribute to GBM's lethality.
- Glioma-associated microglia and macrophages (GAMs) are abundant in GBM and impact prognosis.
Purpose of the Study:
- To review the literature on GAMs' role in GBM biology.
- To discuss pharmacological strategies targeting GAMs for GBM treatment.
Main Methods:
- Extensive literature review using the PubMed database.
- Critical discussion of articles on GAM contribution to GBM and therapeutic modulation.
Main Results:
- GAMs comprise up to 30% of the glioma mass, adopting diverse activation phenotypes (M1/M2).
- GAMs promote tumor growth and invasion via extracellular matrix degradation.
- Pharmacological strategies targeting GAM recruitment, polarization, and function are under development.
Conclusions:
- GAMs significantly contribute to GBM growth and invasiveness.
- Targeting GAMs presents a valuable therapeutic strategy for GBM treatment.
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