EXPLORING 4-METHYILUMBELLIFERONE AS AN IMMUNE MODULATOR IN GLIOBLASTOMA TREATMENT

PIBUEL M; POODTS D; NOLI TRUANT S; REDOLFI D; SIAS S; ROSATO M; BYRNE A.; HAJOS S; FERNANDEZ M; JANCIC C; FRANCO P; LOMPARDÍA S

San Luis

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

SOCIEDAD ARGENTINA DE INMUNOLOGÍA- Universidad Nacional de San Luis

Glioblastoma (GBM) is the most aggressive primary brain tumor presenting therapeuticobstacles due to its complex immune microenvironment. The immune response againstGBM 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 limitedefficacy and adverse effects, underscoring the need for innovative therapies. In light ofthis, we previously demonstrated the anti-tumor effect of 4-methylumbelliferone (4MU), anatural compound without reported adverse effects, on GBM cells.Considering the previous, this study aimed to evaluate the impact of TMZ, 4MU, and theircombination on immune cell populations tied to the anti-GBM response.In vitro assays encompassed BV2 microglial cells, neutrophils, and γδ T cells isolated fromGBM patients. Metabolic activity, cell proliferation, and cell death were assessed throughthe XTT assay, BrdU incorporation, and PI incorporation, respectively. Additionally, wemeasured cytokine secretion (IFN-γ and IL-12) using ELISA and γδ T cell activation byflow cytometry CD69 expression.Our results unveiled significant findings. Both TMZ and 4MU diminished metabolic activityand BV2 microglial cell proliferation (p