Suppression of antitumor immune signatures and upregulation of VEGFA as IDH-mutant gliomas progress to higher grade

Neurosurg Focus. 2024 Feb;56(2):E2. doi: 10.3171/2023.11.FOCUS23694.


Objective: Several studies have compared the immune microenvironment of isocitrate dehydrogenase (IDH)-wildtype glioma versus IDH-mutant glioma. The authors sought to determine whether histological tumor progression in a subset of IDH-mutant glioma was associated with concomitant alterations in the intratumoral immune microenvironment.

Methods: The authors performed bulk RNA sequencing on paired and unpaired samples from patients with IDH-mutant glioma who underwent surgery for tumor progression across multiple timepoints. They 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. The authors 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, the authors 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.

Keywords: cancer microenvironment; immunomodulatory therapy; isocitrate dehydrogenase 1; malignant gliomas; myeloid cells; transcriptome profiling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Astrocytoma* / genetics
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / pathology
  • Brain Neoplasms* / surgery
  • Glioblastoma*
  • Glioma* / genetics
  • Glioma* / pathology
  • Humans
  • Isocitrate Dehydrogenase / genetics
  • Mutation / genetics
  • Tumor Microenvironment / genetics
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism


  • Isocitrate Dehydrogenase
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A