Tacedinaline (CI-994), a class I HDAC inhibitor, targets intrinsic tumor growth and leptomeningeal dissemination in MYC-driven medulloblastoma while making them susceptible to anti-CD47-induced macrophage phagocytosis via NF-kB-TGM2 driven tumor inflammation.
Viktoria MarquardtJohanna TheruvathDavid PauckDaniel PicardNan QinLena BlümelMara MaueJasmin BartlUlvi AhmadovMaike LanginiFrauke-Dorothee MeyerAllison ColeJoselyn Cruz-CruzClaus M GraefMatthias WölflTill MildeOlaf WittAnat Erdreich-EpsteinGabriel LeprivierUlf KahlertAnja StefanskiKai StühlerStephen T KeirDarell D BignerJulia HauerThomas BeezChristiane B Knobbe-ThomsenUte FischerJörg FelsbergFinn K HansenRajeev VibhakarSujatha VenkatramanSamuel H CheshierGuido ReifenbergerArndt BorkhardtThomas KurzMarc RemkeSiddhartha S MitraPublished in: Journal for immunotherapy of cancer (2023)
Together, these findings suggest a dynamic relationship between MYC amplification and innate immune suppression in MYC amplified MB and support further investigation of phagocytosis modulation as a strategy to enhance cancer immunotherapy responses.