biostudies-literatureCornel AMNCI NIH HHSVilla Joep Foundatione005002https://www.ebi.ac.uk/biostudies/studies/S-EPMC9756225biostudies-literatureUnknown10(12)<h4>Background</h4>Immunotherapy in high-risk neuroblastoma (HR-NBL) does not live up to its full potential due to inadequate (adaptive) immune engagement caused by the extensive immunomodulatory capacity of HR-NBL. We aimed to tackle one of the most notable immunomodulatory processes in neuroblastoma (NBL), absence of major histocompatibility complex class I (MHC-I) surface expression, a process greatly limiting cytotoxic T cell engagement. We and others have previously shown that MHC-I expression can be induced by cytokine-driven immune modulation. Here, we aimed to identify tolerable pharmacological repurposing strategies to upregulate MHC-I expression and therewith enhance T cell immunogenicity in NBL.<h4>Methods</h4>Drug repurposing libraries were screened to identify compounds enhancJournal for immunotherapy of cancerEpigenetic modulation of neuroblastoma enhances T cell and NK cell immunogenicity by inducing a tumor-cell lineage switch.PMC9756225R01 CA271605IWOV-Actief.51381.180034Essing AHWHofman DADas SSzanto CSvan den Beemt DAMHLo Presti Vvan den Ham Fvan Heesch SStrijker JGMWienke JNierkens SDunnebach EGeorge REEngels SAGKoopmans BMolenaar JJDierselhuis MPCornel AMSengupta SfalseEpigenetic modulation of neuroblastoma enhances T cell and NK cell immunogenicity by inducing a tumor-cell lineage switch.<h4>Background</h4>Immunotherapy in high-risk neuroblastoma (HR-NBL) does not live up to its full potential due to inadequate (adaptive) immune engagement caused by the extensive immunomodulatory capacity of HR-NBL. We aimed to tackle one of the most notable immunomodulatory processes in neuroblastoma (NBL), absence of major histocompatibility complex class I (MHC-I) surface expression, a process greatly limiting cytotoxic T cell engagement. We and others have previously shown that MHC-I expression can be induced by cytokine-driven immune modulation. Here, we aimed to identify tolerable pharmacological repurposing strategies to upregulate MHC-I expression and therewith enhance T cell immunogenicity in NBL.<h4>Methods</h4>Drug repurposing libraries were screened to identify compounds enhanc2022-01-01T00:00:00Z2022 Dec2026-06-15T06:04:08.551Z2024-11-13T10:37:59.225ZS-EPMC97562253652192710.1136/jitc-2022-005002