Glioblastoma extracellular vesicles modulate immune PD-L1 expression in accessory macrophages upon radiotherapy

Markus W. Schweiger, Zohreh Amoozgar, Pierre Repiton, Robert Morris, Semer Maksoud, Michael Hla, Eric Zaniewski, David P. Noske, Wilhelm Haas, Koen Breyne, Bakhos A. Tannous

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3 Citations (Scopus)

Abstract

Glioblastoma (GBM) is the most aggressive brain tumor, presenting major challenges due to limited treatment options. Standard care includes radiation therapy (RT) to curb tumor growth and alleviate symptoms, but its impact on GBM is limited. In this study, we investigated the effect of RT on immune suppression and whether extracellular vesicles (EVs) originating from GBM and taken up by the tumor microenvironment (TME) contribute to the induced therapeutic resistance. We observed that (1) ionizing radiation increases immune-suppressive markers on GBM cells, (2) macrophages exacerbate immune suppression in the TME by increasing PD-L1 in response to EVs derived from GBM cells which is further modulated by RT, and (3) RT increases CD206-positive macrophages which have the most potential in inducing a pro-oncogenic environment due to their increased uptake of tumor-derived EVs. In conclusion, RT affects GBM resistance by immuno-modulating EVs taken up by myeloid cells in the TME.
Original languageEnglish
Article number108807
JournaliScience
Volume27
Issue number2
DOIs
Publication statusPublished - 16 Feb 2024

Keywords

  • Cancer
  • Cell biology
  • Immunology
  • Proteomics

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