Macrophage Ablation Reduces M2-Like Populations and Jeopardizes Tumor Growth in a

Monocytes/macrophages are an influential component of the glioma microenvironment. However, understanding their diversity and plasticity constitute one of the most challenging areas of research due to the paucity of models to study these cells' inherent complexity. Herein, we analyzed the role of monocytes/macrophages in glioma growth by using a transgenic model that allows for conditional ablation of this cell population. We modeled glioma using intracranial GL261-bearingCSF-1R–GFP + macrophage Fas-induced apoptosis (MAFIA) transgenic mice. Conditional macrophage ablation was achieved by exposure to the dimerizer AP20187. Double immunofluorescence was used tocharacterizeM1-andM2-likemonocytes/macrophagesduringtumorgrowthandafterconditionalablation.During glioma growth, the monocyte/macrophage population consisted predominantly of M2 macrophages. Conditional temporal depletion of macrophages reduced the number of GFP + cells, targeting mainly the repopulation of M2polarized cells, and altered the appearance of M1-like monocytes/macrophages, which suggested a shift in the M1/ M2 macrophage balance. Of interest, compared with control-treated mice, macrophage-depleted mice had a lower tumor mitotic index, microvascular density, and reduced tumor growth. These results demonstrated the possibility ofstudyinginvivotheroleandphenotypeofmacrophagesingliomasandsuggestedthattransitorydepletionofCSF1R + population influences the reconstitutive phenotypic pool of these cells, ultimately suppressing tumor growth. The MAFIA model provides a much needed advance in defining the role of macrophages in gliomas.