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.