EXPLORING 4-METHYILUMBELLIFERONE AS AN IMMUNE MODULATOR IN GLIOBLASTOMA TREATMENT

PIBUEL, MATIAS A; POODTS, DANIELA; NOLI TRUANT, SOFIA; REDOLFI, DANIELA; SIAS, SOFIA; ROSATO, MICAELA; BYRNE, AGUSTÍN; HAJOS, SILVIA E; MARISA M. FERNANDEZ; JANCIC, CAROLINA; FRANCO, PAULA G; LOMPARDIA, SILVINA L

San Luis

Congreso; LXXI Reunión Anual de la Sociedad Argentina de Inmunología; 2023

Sociedad Argentina de Inmunología

Glioblastoma (GBM) is the most aggressive primary brain tumor presenting therapeutic obstacles due to its complex immune microenvironment. The immune response against GBM initiates with microglial cells orchestrating early defenses. Subsequently, the blood-brain barrier's disruption permits neutrophils and γδ T cells to infiltrate the tumor site. Temozolomide (TMZ) remains as the first-line drug for GBM treatment despite limited efficacy and adverse effects, underscoring the need for innovative therapies. In light of this, we previously demonstrated the anti-tumor effect of 4-methylumbelliferone (4MU), a natural compound without reported adverse effects, on GBM cells.Considering the previous, this study aimed to evaluate the impact of TMZ, 4MU, and their combination on immune cell populations tied to the anti-GBM response.In vitro assays encompassed BV2 microglial cells, neutrophils, and γδ T cells isolated from GBM patients. Metabolic activity, cell proliferation, and cell death were assessed through the XTT assay, BrdU incorporation, and PI incorporation, respectively. Additionally, we measured cytokine secretion (IFN-γ and IL-12) using ELISA and γδ T cell activation by flow cytometry CD69 expression.Our results unveiled significant findings. Both TMZ and 4MU diminished metabolic activity and BV2 microglial cell proliferation (p