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

AI Article Synopsis

  • - The study examined how the immune microenvironment changes in IDH-mutant glioma tumors as they progress, comparing it with IDH-wildtype gliomas to understand these differences better.
  • - Using bulk RNA sequencing, researchers analyzed samples from IDH-mutant glioma patients to identify gene expression patterns and immune cell proportions linked to tumor progression over time.
  • - Findings revealed that higher-grade IDH-mutant astrocytomas showed specific gene changes, including increased VEGFA levels, indicating a more aggressive immune environment, which could impact treatment timing for these tumors.

Article Abstract

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.

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Source
http://dx.doi.org/10.3171/2023.11.FOCUS23694DOI Listing

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