IMMU-32. SPERMIDINE DRIVES GLIOBLASTOMA PROGRESSION VIA SELECTIVE MODULATION OF THE IMMUNE SYSTEM

Abstract Glioblastoma (GBM) is incurable despite aggressive standard of care treatments (maximal safe surgical resection, radiation, chemotherapy). GBM therapeutic resistance due to multiple factors, including tumor heterogeneity and a highly immunosuppressive environment. Naturally occurring polyamines have been identified as putative target in other cancers based on their increased presence function normal conditions; they are critical for cell growth proliferation cellular functions autophagy apoptosis. While patients, little known about impact growth. In syngeneic immune competent mouse glioma models (GL261, SB28), mass spectrometry data revealed that spermidine (SPD) – member the polyamine family tissue compared non-neoplastic control brain (sham implanted animals). To test SPD growth, we treated with exogenous found treatment significantly decreased survival. However, immunocompromised host mice, no such difference was observed, indicating mechanism through which driving progression likely involves system alterations. Depletion myeloid derived suppressor cells vivo via anti-Gr-1 antibody rescues decrease survival caused by SPD, drives affecting immune-suppressive subsets, namely MDSCs. assess if associated more human currently analyzing levels samples long vs short term survivors. We also exploring effect dietary gut-brain-microbiome axis, enriched many foods produced subset commensal gut microbes. Understanding interactions between polyamines, microenvironment, response provide new regulation identify opportunities alter environment body enhance immunotherapeutic efficacy.