Loss of retinoic acid signaling drives immune escape in IDH mutant gliomas

Gliomas are immunologically cold tumors that can be broken into several categories based on either RNA expression profiles or methylation profiles, with isocitrate dehydrogenase (IDH) mutations defining a major segregration between types. IDH mutant gliomas often exhibit defects in the retinoic acid pathway. We treated mice harboring IDH mutant gliomas with all-trans retinoic acid, and found that this treatment cause reductions in tumor growth and a swith in immune profiles in the tumor microenvironment. Overall design: Neurospheres (50,000 cells) were injected into the striatium of 6 week old mice. Mice were treated with either 10 mg/kg ATRA or control intra-peritoneally every other day until they were sacrificed based on signs of CNS pathology. 5-prime based single-cell RNAseq was then performed on manually dissected and digested tumors.