IMMU-38. MYC DRIVEN IMMUNE SUPPRESSION IN GROUP 3 MEDULLOBLASTOMA

Abstract BACKGROUND The expression of MYC in tumor cells regulates the microenvironment through innate and adaptive immune effector regulatory cytokines. has also been shown to regulate checkpoint gene products CD47 programmed death-ligand 1 (PD-L1). While PD-L1 inhibits response, on binds SIRPa macrophages acts as a “Don’t eat me” signal. We have previously that blocking CD47-SIRPa pathway significantly decreases burden increases survival five etiologically distinct adult pediatric brain xenograft models, including Group 3 or MYC-driven MB, by activating macrophage-mediated phagocytosis. METHODS performed primary screen 78 epigenetic inhibitors secondary 20 histone deacetylase (HDACi) compare response profiles ATRT, medulloblastoma (n = 14), glioblastoma 14). This unbiased approach revealed preferential activity Class I HDACi mediated induction apoptosis, reduction transcription, release pro-inflammatory cytokines medulloblastoma, with little no non-MYC-driven AT/RT, vitro. In addition, we tested combinatorial effect directly targeting MYC/MAX interaction using MYCI-975 phagocytosis in-vitro assays in-vivo models. two orthotopic mouse models MYCi975 displayed anti-tumoral effects at site metastatic compartment. Furthermore, RNA sequencing NFκB treatment, followed interferon-gamma (IFN-G) cell surface engulfment (“eat-me”) signals (such calreticulin) enhanced vitro tumor-bearing mice. CONCLUSION Together, these findings suggest dynamic relationship between amplification suppression MYC-medulloblastoma support further investigation modulation strategy enhance cancer immunotherapy responses.