REVIEW article
Front. Immunol.
Sec. Multiple Sclerosis and Neuroimmunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1472710
Rational therapeutic targeting of myeloid cells in glioblastoma: Challenges and perspectives
Provisionally accepted
Maya Saleh*
Faruk Akay- Institut National de la Recherche Scientifique, Université du Québec, Quebec City, Quebec, Canada
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Glioblastoma (GB) is the most aggressive tumor of the central nervous system (CNS), accounting for almost 80% of all primary brain tumors. Despite standard-of-care consisting of surgical resection, when possible, adjuvant radiotherapy (RT) and chemotherapy with Temozolomide (TMZ), GB remains highly fatal, with an estimated recurrence rate of over 90% and a median overall survival (OS) of around 15 months from diagnosis. Several factors contribute to such poor patient outcome, including a unique myeloid-rich tumor microenvironment (TME) that confers immunosuppression and therapeutic resistance.Multi-omics, single-cell transcriptomics and multi-modal spatial analyses of GB are unraveling the diversity of brain myeloid cells, including activated microglia, borderassociated macrophages (BAM), and monocyte-derived glioma-associated macrophages (GAM), instructed by ontogeny, spatial distribution, cell-cell interactions and response to metabolic cues in the TME. In this review, we elaborate on the heterogeneity and plasticity of myeloid cells in GB and discuss the promise and challenges for rational therapeutic targeting of GAMs in GB.
Keywords: Central Nervous System, Glioblastoma, Tumor Microenvironment, innate immunity, Myeloid Cells, Glioma-associated macrophages, Immunotherapy, clinical trials
Received: 29 Jul 2024; Accepted: 05 Jun 2025.
Copyright: © 2025 Saleh and Akay. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Maya Saleh, Institut National de la Recherche Scientifique, Université du Québec, Quebec City, G1K 9A9, Quebec, Canada
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.