1349 Suppression of Antitumor Immune Signatures and Upregulation of VEGFA as IDH-Mutant Gliomas Progress to Higher Grade

INTRODUCTION: Several studies have compared the immune microenvironment of isocitrate dehydrogenase (IDH)–wildtype glioma versus IDH-mutant glioma. However, how this microenvironment shifts with progression events and changes as tumors increase in grade has been underexplored to date. METHODS: We performed bulk RNA sequencing on paired and unpaired samples from patients with IDH-mutant glioma who underwent surgery for tumor progression across multiple timepoints. We compared patterns of differential gene expression, overall inflammatory signatures, and transcriptomic measures of relative immune cell proportions. RESULTS: A total of 55 unique IDH-mutant glioma samples were included in the analysis. We identified multiple genes associated with progression and higher grade across IDH-mutant oligodendrogliomas and astrocytomas. Compared with lower-grade paired samples, grade 4 IDH-mutant astrocytomas uniquely demonstrated upregulation of VEGFA in addition to counterproductive alterations in inflammatory score reflective of a more hostile immune microenvironment. CONCLUSIONS: Here, we have provided a transcriptomic analysis of a progression cohort for IDH-mutant glioma. Compared with lower-grade tumors, grade 4 astrocytomas displayed alterations that may inform the timing of antiangiogenic and immune-based therapy as these tumors progress.