Aparna Rao, Xiaoran Zhang, Anthony R Cillo, Jonathan H Sussman, Poorva Sandlesh, Antonio Corral Tarbay, Arka N Mallela, Carly Cardello, Katharine Krueger, Jessica Xu, Alex Li, Jason Xu, Jonathan Patterson, Ebrar Akca, Angelo Angione, Emade Jaman, Wi Jin Kim, Jordan Allen, Abhishek Venketeswaran, Pascal O Zinn, Robert Parise, Jan Beumer, Anette Duensing, Eric C Holland, Robert Ferris, Stephen J Bagley, Tullia C Bruno, Dario A A Vignali, Sameer Agnihotri, Nduka M Amankulor
Diffuse gliomas are epigenetically dysregulated, immunologically cold, and fatal tumors characterized by mutations in isocitrate dehydrogenase (IDH). Although IDH mutations yield a uniquely immunosuppressive tumor microenvironment, the regulatory mechanisms that drive the immune landscape of IDH mutant (IDHm) gliomas remain unknown. Here, we reveal that transcriptional repression of retinoic acid (RA) pathway signaling impairs both innate and adaptive immune surveillance in IDHm glioma through epigenetic silencing of retinol binding protein 1 (RBP1) and induces a profound anti-inflammatory landscape marked by loss of inflammatory cell states and infiltration of suppressive myeloid phenotypes...
April 13, 2024: bioRxiv