Extracellular Vesicles in Glioblastoma: Insights and Implications for Novel Therapeutic Strategies

This thesis aims to advance our understanding of how EVs contribute to the pathogenesis and treatment resistance of GBM with the goal of informing future treatment and research. In the first part of the thesis, we examine GBM and analyze the pre-clinical models used for studying its properties (Chapter 2). Furthermore, we investigate EVs and evaluate methodologies for tracking them (Chapter 3). In the second part, we explore the role of EVs on the GBM TME. First, we examine the effects of EVs on intratumoral heterogeneity in GBM, highlighting their role in increased invasiveness and therapeutic resistance (Chapter 4). Next, we try to understand the effect of EVs on immune cells in the TME, focusing on myeloid cells, the most prevalent one (Chapter 5). We demonstrate how GBM EVs induce a tumor-associated phenotype in recipient myeloid cells and investigate this in the context of radiation. In the third part, we synthesize insights from Part 1 and Part 2 to devise a novel AAV-based gene therapy approach against GBM (Chapter 6). In the fourth part, we investigate how olfactory receptors expressed on cancer cells modulate invasion, migration, and metastasis, which resulted in the proposition of olfactory receptor 5B21 as a novel oncogene (Chapter 7). In the final section, we discuss the core findings, point out limitations, and provide recommendations for future studies (Chapter 8).