Characterization of a pathogenic subpopulation of human glioma associated macrophages linked to glioma progression

Primary de novo high grade gliomas, such as glioblastoma and lower grade gliomas both converge on a common aggressive phenotype, and the basis for this progression is unknown. Glioma associated macrophages (GAM) have been strongly implicated in supporting tumor growth, however, robust isolation of functional subpopulations has been elusive. We hypothesize that functional populations of GAMs can be resolved through gene regulatory network (GRN) inference and show that a subpopulation of human GAMs, defined by a GRN centered around the activator protein-1 transcription factor FOSL2 is preferentially enriched in high grade gliomas. We nominate ANXA1 and HMOX1 as surrogate cell surface markers for a subpopulation we term malignancy associated GAMs (mGAMs) which possess distinct pro-tumorigenic properties, share partial ontogeny with peripheral blood monocytes, and are enriched in newly transformed regions of glioma. mGAMs potentially play a pivotal role in glioma progression and represent a plausible therapeutic target.