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In vitro generated macrophages reflect the immunosuppressive phenotype of in vivo glioblastoma-associated macrophages

Matthew Nazzaro,Elaine R. Mardis,M. Artomov,E. Juenger,Justin Lyberger,Mark A. Damante,Gregory Behbehani,S. Sarkar,P. Rajappa

Published 2026 in Oncoimmunology

ABSTRACT

ABSTRACT Glioblastoma (GBM) is the most common primary central nervous system tumor with a dismal prognosis and limited treatment options. Recent success utilizing immunotherapies for treating other solid tumors have been largely unsuccessful in GBM. One of the primary mechanisms of GBM immunotherapeutic resistance is because of excessive infiltration of myeloid cells that create an immunosuppressive tumor microenvironment (TME). Among these infiltrating myeloid cells, tumor-associated macrophages (TAMs), comprise a substantial portion of the TME and are associated with poor prognosis in GBM patients. Researchers have only recently begun to dissect the dynamics and complexity of TAMs. However, reliable and reproducible translational methods for generating GBM TAMs in vitro are lacking. Here, we have investigated an in vitro, reproducible murine-based model for bone marrow-derived, glioma-educated macrophages (gTAMs) and performed rigorous analysis to expand our understanding of gTAMs to provide a validated tool for investigating therapeutic response.

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