TMIC-43. Tumor-Associated Neutrophils: A Double-Edged Sword in Glioblastoma Progression

Abstract INTRODUCTION Tumor-associated myeloid populations contribute significantly to immunosuppression and treatment resistance in glioblastoma (GBM). While the pro-tumorigenic influence of tumor-associated neutrophils (TANs)—including their role in promoting angiogenesis, immunosuppression, and immune checkpoint expression—is well documented, their potential anti-tumoral functions remain insufficiently investigated. METHODS This study employed CT2A syngeneic murine models of GBM to investigate the immunological and oncological consequences of systemic neutrophil depletion. Anti-Ly6G antibodies were administered intraperitoneally to selectively eliminate circulating neutrophils. Tumor progression was monitored through in vivo bioluminescence imaging (IVIS), while immune profiling was conducted using flow cytometry on samples from the brain, blood, and spleen. RESULTS Over a 21-day period, IVIS imaging revealed signficantly elevated radiance in neutrophil-depleted mice relative to controls, indicating enhanced tumor burden (mean radiance fold-change: 2.7; p = 0.042). Kaplan-Meier analysis showed that neutrophil-depleted animals had significantly shortened survival (median: 19 vs. 24 days; log-rank p = 0.0058). Importantly, this reduction in survival was not observed in neutrophil-depleted mice lacking tumors, suggesting that the neutrophil effect is context-dependent within the GBM tumor microenvironment (TME). Flow cytometric analysis confirmed effective peripheral neutrophil depletion, with CD45⁺Ly6G⁺CD11b⁺ cells reduced from 3.1% to 0.03% (p < 0.001). Additionally, a trend toward reduced brain-infiltrating CD8⁺ T cells was observed in the absence of neutrophils (p = 0.0553). CONCLUSION Our findings present one of the first reported pre-clinical evidence that TANs may exert protective, anti-tumoral effects within the GBM TME. Neutrophil depletion not only accelerated tumor progression and impaired survival but also disrupted immune equilibrium in the brain. These data support a paradigm shift in which TANs may be leveraged or reprogrammed as therapeutic agents in future GBM immunotherapies. Continued investigation is warranted to delineate the molecular basis of TAN plasticity and their potential role in reshaping anti-GBM immunity.