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Spatially Resolved Microglia/Macrophages in Recurrent Glioblastomas Overexpress Fatty Acid Metabolism and Phagocytic

Akshitkumar M Mistry1,2, Jonah Daneshmand3, SeonYeong Jamie Seo1

  • 1Department of Neurosurgery, University of Louisville, Louisville, KY 40202, USA.

Current Oncology (Toronto, Ont.)
|March 27, 2024
PubMed
Abstract

Insights

Tumor-associated microglia/macrophages in recurrent glioblastoma (GBM) show increased fatty acid and lipid metabolism gene expression. The lipid metabolism gene PLD3 correlates with survival in GBM patients.

Area of Science:

  • Neuro-oncology
  • Cancer immunology
  • Genomics

Background:

  • Glioblastoma (GBM) tumors feature abundant tumor-associated microglia/macrophages.
  • Understanding treatment-induced changes in these cells is crucial.
  • This study investigates gene expression shifts in microglia/macrophages (Iba1+) between de novo and recurrent GBMs.

Purpose of the Study:

  • To analyze gene expression changes in microglia/macrophages (Iba1+) and glial cells (Gfap+) in de novo versus recurrent GBM.
  • To identify key genes and pathways altered during GBM recurrence.
  • To assess the correlation of differentially expressed genes with patient survival.

Main Methods:

  • NanoString GeoMx® Digital Spatial Transcriptomic Profiling was employed on paired de novo and recurrent GBM samples.
  • Microglia/macrophages (Iba1+) and glial cells (Gfap+) were analyzed.
  • Publicly available datasets were used to evaluate the impact of gene expression on patient survival.

Main Results:

  • Transcriptomic data revealed distinct clustering of Iba1+ and Gfap+ cells.
  • Immune-function genes were upregulated in Iba1+ cells compared to Gfap+ cells.
  • Recurrent GBM samples showed upregulation of phagocytosis and fatty acid/lipid metabolism genes in Iba1+ cells, with PLD3 strongly correlating with survival.

Conclusions:

  • Recurrent GBM microglia/macrophages exhibit overexpression of genes related to fatty acid/lipid metabolism.
  • The gene PLD3 is a potential prognostic marker in GBM.
  • Further research into PLD phospholipases' role in GBM progression is warranted.
Keywords:
fatty acidglioblastomamacrophagesmicrogliarecurrence

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