TAMI-57. INDUCTION OF FERROPTOSIS PROMOTES IMMUNOGENIC CELL DEATH AND ACTIVATION OF THE IMMUNE MICROENVIRONMENT IN GLIOMA

Abstract Gliomas are immune cold tumors. Effective therapeutic strategies capable of inducing an response lacking.Here we present evidence that ferroptosis, a form iron-mediated lipid peroxidation-based cell death, may promote anti-tumor immunity via stimulation phagocytosis and pro-inflammatory activities in microglia. While ferroptosis has shown promise induction glioma the immunogenic microenvironmental effects poorly understood. First, tested vitro glutathione peroxidase 4 (GPX4) inhibitor RSL3, inducer, on murine lines. Using flow cytometry, discovered RSL3 treatment led to membrane translocation pro-phagocytic antigen calreticulin, known hallmark by average log2-fold-change 2.53 (p= 0.03) compared DMSO-treated controls. This effect correlated with peroxidation, as assessed BODIPY-C11 staining. To further test cell-microglia crosstalk, prepared acute brain tumor slices from both mouse human samples, treated them RSL3. Quantification immunofluorescent staining three independent slice cultures after demonstrated significant increase calreticulin abundance control (p < 0.001). Importantly, this was significantly diminished addition ferrostatin, demonstrating directly responsible for translocation. Single-cell RNAseq overexpression population, positive enrichment interferon signaling, presentation, ontologies myeloid compartments. These findings suggest ferroptosis-induced surface cells promotes activation local microenvironment increasing presentation cytokine release tumor-associated Thus, ferroptosis-inducing drugs through death signals.