Glioblastoma extracellular vesicles modulate immune PD-L1 expression in accessory macrophages upon radiotherapy
Summary: 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 o...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224000282 |
| _version_ | 1797350640162177024 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Markus W. Schweiger |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-03-08T12:47:48Z |
| format | Article |
| id | doaj.art-db23f5ee32a4459ab10e27118100af65 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-08T12:47:48Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-db23f5ee32a4459ab10e27118100af652024-01-21T05:09:52ZengElsevieriScience2589-00422024-02-01272108807Glioblastoma extracellular vesicles modulate immune PD-L1 expression in accessory macrophages upon radiotherapyMarkus W. Schweiger0Zohreh Amoozgar1Pierre Repiton2Robert Morris3Semer Maksoud4Michael Hla5Eric Zaniewski6David P. Noske7Wilhelm Haas8Koen Breyne9Bakhos A. Tannous10Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA; Neuroscience Program, Harvard Medical School, Boston, MA 02129, USA; Amsterdam UMC Location Vrije Universiteit Amsterdam, Department of Neurosurgery, 1081 HV Amsterdam, the Netherlands; Cancer Center Amsterdam, Brain Tumor Center and Liquid Biopsy Center, 1081 HV Amsterdam, the NetherlandsDepartment of Radiation Oncology, Edwin L. Steele Laboratories, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USADepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA; Neuroscience Program, Harvard Medical School, Boston, MA 02129, USA; Section of Pharmaceutical Sciences, Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, 1205 Geneva, SwitzerlandMassachusetts General Hospital Cancer Center, Boston, MA 02129, USADepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA; Neuroscience Program, Harvard Medical School, Boston, MA 02129, USADepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA; Neuroscience Program, Harvard Medical School, Boston, MA 02129, USAMassachusetts General Hospital Cancer Center, Boston, MA 02129, USAAmsterdam UMC Location Vrije Universiteit Amsterdam, Department of Neurosurgery, 1081 HV Amsterdam, the Netherlands; Cancer Center Amsterdam, Brain Tumor Center and Liquid Biopsy Center, 1081 HV Amsterdam, the NetherlandsMassachusetts General Hospital Cancer Center, Boston, MA 02129, USA; Department of Medicine, Harvard Medical School, Boston, MA 02129, USADepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA; Neuroscience Program, Harvard Medical School, Boston, MA 02129, USA; Corresponding authorDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA; Neuroscience Program, Harvard Medical School, Boston, MA 02129, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004224000282ImmunologyCell biologyCancerProteomics |
| spellingShingle | 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 Glioblastoma extracellular vesicles modulate immune PD-L1 expression in accessory macrophages upon radiotherapy iScience Immunology Cell biology Cancer Proteomics |
| title | Glioblastoma extracellular vesicles modulate immune PD-L1 expression in accessory macrophages upon radiotherapy |
| title_full | Glioblastoma extracellular vesicles modulate immune PD-L1 expression in accessory macrophages upon radiotherapy |
| title_fullStr | Glioblastoma extracellular vesicles modulate immune PD-L1 expression in accessory macrophages upon radiotherapy |
| title_full_unstemmed | Glioblastoma extracellular vesicles modulate immune PD-L1 expression in accessory macrophages upon radiotherapy |
| title_short | Glioblastoma extracellular vesicles modulate immune PD-L1 expression in accessory macrophages upon radiotherapy |
| title_sort | glioblastoma extracellular vesicles modulate immune pd l1 expression in accessory macrophages upon radiotherapy |
| topic | Immunology Cell biology Cancer Proteomics |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224000282 |
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