Role of extracellular vesicles in immune modulation, angiogenesis, progression and therapeutic resistance of glioblastoma

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor in adults, with a poor prognosis and high recurrence rates despite advancements in treatment. The tumor microenvironment (TME) of GBM is very complex and includes various cell types, such as immune cells, endothelial cells, ast...

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Main Authors: Muhammad Izhar, Ahed H. Kattaa, Amirhossein Akhavan-Sigari, Elaheh Shaghaghian, Yusuke S. Hori, Fred C. Lam, Deyaaldeen AbuReesh, Sara C. Emrich, Louisa Ustrzynski, Armine Tayag, Steven D. Chang, David J. Park
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Extracellular Vesicle
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Online Access:http://www.sciencedirect.com/science/article/pii/S2773041725000113
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author Muhammad Izhar
Ahed H. Kattaa
Amirhossein Akhavan-Sigari
Elaheh Shaghaghian
Yusuke S. Hori
Fred C. Lam
Deyaaldeen AbuReesh
Sara C. Emrich
Louisa Ustrzynski
Armine Tayag
Steven D. Chang
David J. Park
author_facet Muhammad Izhar
Ahed H. Kattaa
Amirhossein Akhavan-Sigari
Elaheh Shaghaghian
Yusuke S. Hori
Fred C. Lam
Deyaaldeen AbuReesh
Sara C. Emrich
Louisa Ustrzynski
Armine Tayag
Steven D. Chang
David J. Park
author_sort Muhammad Izhar
collection DOAJ
description Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor in adults, with a poor prognosis and high recurrence rates despite advancements in treatment. The tumor microenvironment (TME) of GBM is very complex and includes various cell types, such as immune cells, endothelial cells, astrocytes, and microglia. The TME plays a crucial role in the development of GBM and its resistance to therapy. One important part of the TME is extracellular vesicles (EVs), which help cells communicate and contribute to different aspects of GBM progression. They help the tumor grow and spread by increasing cellular proliferation, invasion, and survival. They also play a key role in angiogenesis by transferring pro-angiogenic factors to endothelial cells, which help form new blood vessels that provide the tumor with essential nutrients and oxygen. Within the context of immune modulation, EVs derived from GBM cells contain immunosuppressive molecules that alter the function of immune cells in the TME, enabling the tumor to escape immune surveillance. This immunosuppressive environment is marked by elevated levels of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs). Furthermore, EVs contribute to therapeutic resistance by transferring drug-resistance factors from resistant to sensitive tumor cells, enhancing their capacity to withstand chemotherapy and radiotherapy. The RNA cargo of EVs, which includes microRNAs and long non-coding RNAs, plays a crucial role in modulating gene expression and cellular responses to treatment. In conclusion, EVs are vital in the development and progression of GBM by influencing angiogenesis, immune modulation, and therapeutic resistance. Targeting EV-mediated communication presents a promising therapeutic strategy for addressing the challenges posed by this deadly brain tumor.
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spelling doaj-art-65571ee7e8704e7a89937b9bf0fe481d2025-08-20T03:46:58ZengElsevierExtracellular Vesicle2773-04172025-06-01510007510.1016/j.vesic.2025.100075Role of extracellular vesicles in immune modulation, angiogenesis, progression and therapeutic resistance of glioblastomaMuhammad Izhar0Ahed H. Kattaa1Amirhossein Akhavan-Sigari2Elaheh Shaghaghian3Yusuke S. Hori4Fred C. Lam5Deyaaldeen AbuReesh6Sara C. Emrich7Louisa Ustrzynski8Armine Tayag9Steven D. Chang10David J. Park11Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USADepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USADepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USADepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USADepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USADepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USADepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USADepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USADepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USADepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USADepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USACorresponding author.; Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USAGlioblastoma multiforme (GBM) is the most aggressive primary brain tumor in adults, with a poor prognosis and high recurrence rates despite advancements in treatment. The tumor microenvironment (TME) of GBM is very complex and includes various cell types, such as immune cells, endothelial cells, astrocytes, and microglia. The TME plays a crucial role in the development of GBM and its resistance to therapy. One important part of the TME is extracellular vesicles (EVs), which help cells communicate and contribute to different aspects of GBM progression. They help the tumor grow and spread by increasing cellular proliferation, invasion, and survival. They also play a key role in angiogenesis by transferring pro-angiogenic factors to endothelial cells, which help form new blood vessels that provide the tumor with essential nutrients and oxygen. Within the context of immune modulation, EVs derived from GBM cells contain immunosuppressive molecules that alter the function of immune cells in the TME, enabling the tumor to escape immune surveillance. This immunosuppressive environment is marked by elevated levels of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs). Furthermore, EVs contribute to therapeutic resistance by transferring drug-resistance factors from resistant to sensitive tumor cells, enhancing their capacity to withstand chemotherapy and radiotherapy. The RNA cargo of EVs, which includes microRNAs and long non-coding RNAs, plays a crucial role in modulating gene expression and cellular responses to treatment. In conclusion, EVs are vital in the development and progression of GBM by influencing angiogenesis, immune modulation, and therapeutic resistance. Targeting EV-mediated communication presents a promising therapeutic strategy for addressing the challenges posed by this deadly brain tumor.http://www.sciencedirect.com/science/article/pii/S2773041725000113Extracellular vesiclesExosomesGlioblastomaTherapeutic resistanceGBMImmune resistance
spellingShingle Muhammad Izhar
Ahed H. Kattaa
Amirhossein Akhavan-Sigari
Elaheh Shaghaghian
Yusuke S. Hori
Fred C. Lam
Deyaaldeen AbuReesh
Sara C. Emrich
Louisa Ustrzynski
Armine Tayag
Steven D. Chang
David J. Park
Role of extracellular vesicles in immune modulation, angiogenesis, progression and therapeutic resistance of glioblastoma
Extracellular Vesicle
Extracellular vesicles
Exosomes
Glioblastoma
Therapeutic resistance
GBM
Immune resistance
title Role of extracellular vesicles in immune modulation, angiogenesis, progression and therapeutic resistance of glioblastoma
title_full Role of extracellular vesicles in immune modulation, angiogenesis, progression and therapeutic resistance of glioblastoma
title_fullStr Role of extracellular vesicles in immune modulation, angiogenesis, progression and therapeutic resistance of glioblastoma
title_full_unstemmed Role of extracellular vesicles in immune modulation, angiogenesis, progression and therapeutic resistance of glioblastoma
title_short Role of extracellular vesicles in immune modulation, angiogenesis, progression and therapeutic resistance of glioblastoma
title_sort role of extracellular vesicles in immune modulation angiogenesis progression and therapeutic resistance of glioblastoma
topic Extracellular vesicles
Exosomes
Glioblastoma
Therapeutic resistance
GBM
Immune resistance
url http://www.sciencedirect.com/science/article/pii/S2773041725000113
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