Role of Neuroinflammation in Brain Tumor Progression: Microglia–Astrocyte Crosstalk as a Therapeutic Target

Background: Glioblastoma is one of the most aggressive primary brain tumors, characterized by poor prognosis, high recurrence rates, and limited therapeutic success. Increasing evidence indicates that neuroinflammation plays a crucial role in shaping the tumor microenvironment and promoting disease progression. Microglia and astrocytes, the principal glial cells of the central nervous system, undergo tumor-induced activation and contribute to tumor growth, immune evasion, angiogenesis, and therapy resistance.

Objective: To investigate the role of microglia–astrocyte crosstalk in driving neuroinflammation during brain tumor progression and to identify potential therapeutic targets within the tumor microenvironment.

Methods: A literature-based analysis was conducted focusing on recent findings regarding glial cell interactions, inflammatory signaling pathways, and their contribution to glioma progression.

Results: Tumor-derived signals activate microglia, leading to the release of pro-inflammatory cytokines such as IL-1β and TNF-α. These cytokines stimulate astrocyte activation, resulting in the secretion of IL-10, TGF-β, and VEGF. This feedback loop sustains chronic neuroinflammation, promotes tumor invasion and migration, suppresses anti-tumor immunity, enhances angiogenesis, and contributes to resistance against chemotherapy and radiotherapy. Several therapeutic strategies targeting this axis, including CSF1R inhibitors, JAK/STAT inhibitors, TGF-β pathway inhibitors, CCL2/CCR2 blockade, Connexin-43 inhibitors, extracellular vesicle targeting, and immune checkpoint inhibitors, show promising potential.

Conclusion: Microglia–astrocyte crosstalk is a critical driver of neuroinflammation and glioblastoma progression. Targeting both tumor cells and the surrounding neuroinflammatory microenvironment may provide a more effective therapeutic strategy for precision neuro-oncology. Future research should focus on biomarker-guided therapies, single-cell and spatial omics approaches, and improved blood–brain barrier drug delivery systems.

Keywords: Glioblastoma, Neuroinflammation, Microglia, Astrocytes, Tumor Microenvironment, Cytokines, Immune Evasion, Therapy Resistance, Neuro-Oncology.