P09.02 Epigenetic modulation of neuroblastoma enhances T- and NK cell immunogenicity via induction of surface expression of MHC class I and MICA/MICB

Background Neuroblastoma (NBL) is the most common pediatric solid tumor and responsible for about 15% of all cancer deaths. The majority high-risk (HR) patients suffers from relapse after intense therapy regimens, resulting in a 5-year survival rate only 40%. Even though potential immune interference HR-NBL shown by additive effect anti-GD2 monoclonal antibody to treatment protocol, long-term follow-up studies reveal that beneficial immunotherapy diminishes over time. We hypothesize this result inadequate (adaptive) engagement caused extensive immunomodulatory capacity its microenvironment. One remarkable strategies NBL tumors absence MHC-I surface expression, thereby preventing cytotoxic T cell recognition killing. lacking cells are known be subjected NK mediated cytotoxicity, however, we have able evade temporary upregulating expression MHC-I, becoming temporarily more prone cytotoxicity. aim project identify pharmacological enhance adaptive activation therewith immunogenicity HR-NBL. Materials Methods FDA-approved drug libraries were screened compounds enhancing lines using high-throughput flow cytometry analyses optimized adherent cells. positive hits was subsequently confirmed panel patient-derived tumeroids. Alterations transcriptome translatome upon incubation with interest further studied additional effects NBL. Ultimately, compound treated tumeroids co-cultured PRAME reactive tumor-specific healthy-donor determine vitro on T- Results Drug library screening revealed upregulation multiple histon deacetylase inhibitors (HDACi). Further investigation HDACi enhanced several players antigen presenting machinery, immunoproteasome MICA/MICB show untreated cells, plasticity causes evasion both NK- Intriguingly, co-culture Entinostat resulted Conclusions other machinery players, NKG2D ligands Pre-treatment substantiating as strategy improve aid treatment. This work supported Villa Joep Foundation [IWOV-Actief.51391.180034]. Disclosure Information A.M. Cornel: None. D.A.M.H. van den Beemt: E. Dunnebach: M.P. Dierselhuis: S. Nierkens: