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Media type:
E-Article
Title:
Gamma Irradiation Triggers Immune Escape in Glioma-Propagating Cells
Contributor:
Hoppmann, Nicola;
Heinig, Nora;
Distler, Ute;
Kim, Ella;
Lennerz, Volker;
Krauß, Yvonne;
Schumann, Ulrike;
Giese, Alf;
Tenzer, Stefan;
Bitar, Lynn;
Schmidt, Mirko H. H.
Published:
MDPI AG, 2022
Published in:
Cancers, 14 (2022) 11, Seite 2728
Language:
English
DOI:
10.3390/cancers14112728
ISSN:
2072-6694
Origination:
Footnote:
Description:
Glioblastoma multiforme is the most common and devastating form of brain tumor for which only palliative radio- and chemotherapy exists. Although some clinical studies on vaccination approaches have shown promising efficacy due to their potential to generate long-term immune surveillance against cancer cells, the evasion mechanisms preventing therapy response are largely uncharacterized. Here, we studied the response of glioblastoma-propagating cells (GPCs) to clinically relevant doses of γ radiation. GPCs were treated with 2.5 Gy of γ radiation in seven consecutive cellular passages to select for GPCs with increased colony-forming properties and intrinsic or radiation-induced resistance (rsGPCs). Quantitative proteomic analysis of the cellular signaling platforms of the detergent-resistant membranes (lipid rafts) in GPCs vs. rsGPCs revealed a downregulation of the MHC class I antigen-processing and -presentation machinery. Importantly, the radio-selected GPCs showed reduced susceptibility towards cytotoxic CD8+ T-cell-mediated killing. While previous studies suggested that high-dose irradiation results in enhanced antigen presentation, we demonstrated that clinically relevant sub-lethal fractionated irradiation results in reduced expression of components of the MHC class I antigen-processing and -presentation pathway leading to immune escape.