Macrophage Ablation Reduces M2-Like Populations and Jeopardizes Tumor Growth in a MAFIA-Based Glioma Model.
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-bearing CSF-1R-GFP(+) macrophage Fas-induced apoptosis (MAFIA) transgenic mice. Conditional macrophage ablation was achieved by exposure to the dimerizer AP20187. Double immunofluorescence was used to characterize M1- and M2-like monocytes/macrophages during tumor growth and after conditional ablation. 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 M2-polarized 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 of studying in vivo the role and phenotype of macrophages in gliomas and suggested that transitory depletion of CSF-1R(+) 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.
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Konrad
K
Gabrusiewicz
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Mohammad B
MB
Hossain
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nahir
N
Cortes-Santiago
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Xuejun
X
Fan
Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.
Bozena
B
Kaminska
Comprehensive Cancer Center, Wake Forest University, Winston-Salem, NC, USA.
Frank C
FC
Marini
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Juan
J
Fueyo
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. Electronic address: cmanzano@mdanderson.org.
Candelaria
C
Gomez-Manzano
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000378:metabolism / Q000473:pathology; D019014:fas Receptor / Q000378:metabolism
C491899:Fas protein, mouse; D019014:fas Receptor