Acquisition of Immune Privilege in GBM Tumors: Role of Prostaglandins and Bile Salts

Martyn A. Sharpe, David S. Baskin, Ryan D. Johnson, Alexandra M. Baskin

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Based on the postulate that glioblastoma (GBM) tumors generate anti-inflammatory prostaglandins and bile salts to gain immune privilege, we analyzed 712 tumors in-silico from three GBM transcriptome databases for prostaglandin and bile synthesis/signaling enzyme-transcript markers. A pan-database correlation analysis was performed to identify cell-specific signal generation and downstream effects. The tumors were stratified by their ability to generate prostaglandins, their competency in bile salt synthesis, and the presence of bile acid receptors nuclear receptor subfamily 1, group H, member 4 (NR1H4) and G protein-coupled bile acid receptor 1 (GPBAR1). The survival analysis indicates that tumors capable of prostaglandin and/or bile salt synthesis are linked to poor outcomes. Tumor prostaglandin D2 and F2 syntheses are derived from infiltrating microglia, whereas prostaglandin E2 synthesis is derived from neutrophils. GBMs drive the microglial synthesis of PGD2/F2 by releasing/activating complement system component C3a. GBM expression of sperm-associated heat-shock proteins appears to stimulate neutrophilic PGE2 synthesis. The tumors that generate bile and express high levels of bile receptor NR1H4 have a fetal liver phenotype and a RORC-Treg infiltration signature. The bile-generating tumors that express high levels of GPBAR1 are infiltrated with immunosuppressive microglia/macrophage/myeloid-derived suppressor cells. These findings provide insight into how GBMs generate immune privilege and may explain the failure of checkpoint inhibitor therapy and provide novel targets for treatment.

Original languageEnglish (US)
Article number3198
JournalInternational journal of molecular sciences
Issue number4
StatePublished - Feb 6 2023


  • bile
  • glioblastoma (GBM)
  • microglia
  • myeloid-derived suppressor cells
  • prostaglandins
  • regulatory T-cells (Tregs)
  • sperm
  • tumor-associated macrophages

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


Dive into the research topics of 'Acquisition of Immune Privilege in GBM Tumors: Role of Prostaglandins and Bile Salts'. Together they form a unique fingerprint.

Cite this