Rational therapeutic targeting of myeloid cells in glioblastoma: challenges and perspectives

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...

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Main Authors: Faruk Akay, Maya Saleh
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1472710/full
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author Faruk Akay
Maya Saleh
author_facet Faruk Akay
Maya Saleh
author_sort Faruk Akay
collection DOAJ
description 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, border-associated 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.
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spelling doaj-art-8cd71c0d82d64c6090811af11a6026c52025-08-20T03:30:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.14727101472710Rational therapeutic targeting of myeloid cells in glioblastoma: challenges and perspectivesFaruk AkayMaya SalehGlioblastoma (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, border-associated 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1472710/fullcentral nervous systemglioblastomatumor microenvironmentinnate immunitymyeloid cellsglioma-associated macrophages
spellingShingle Faruk Akay
Maya Saleh
Rational therapeutic targeting of myeloid cells in glioblastoma: challenges and perspectives
Frontiers in Immunology
central nervous system
glioblastoma
tumor microenvironment
innate immunity
myeloid cells
glioma-associated macrophages
title Rational therapeutic targeting of myeloid cells in glioblastoma: challenges and perspectives
title_full Rational therapeutic targeting of myeloid cells in glioblastoma: challenges and perspectives
title_fullStr Rational therapeutic targeting of myeloid cells in glioblastoma: challenges and perspectives
title_full_unstemmed Rational therapeutic targeting of myeloid cells in glioblastoma: challenges and perspectives
title_short Rational therapeutic targeting of myeloid cells in glioblastoma: challenges and perspectives
title_sort rational therapeutic targeting of myeloid cells in glioblastoma challenges and perspectives
topic central nervous system
glioblastoma
tumor microenvironment
innate immunity
myeloid cells
glioma-associated macrophages
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1472710/full
work_keys_str_mv AT farukakay rationaltherapeutictargetingofmyeloidcellsinglioblastomachallengesandperspectives
AT mayasaleh rationaltherapeutictargetingofmyeloidcellsinglioblastomachallengesandperspectives