Extracellular Vesicles and the Glioblastoma Microenvironment

Abstract

This thesis describes experiments performed to analyze the role of extracellular vesicles in the microenvironment of glioblastoma tumors. Glioblastoma tumors are both the most common and most lethal primary brain tumors in adult patients. In the glioblastoma tumors multiple non-tumor cells perform different tasks to support the tumor. Among those are cells from the innate immune system including microglia, monocytes and macrophages. One of the modes of communication between the tumor cells and the immune cells is through extracellular vesicles (EVs). EVs are nano-sized vesicles that contain (m)RNAs, proteints and lipids derived from their cell of origin. Glioblastoma derived EVs can transfer oncogenic information to the cells of the immune system. Here, results from experiments are described investigating different tools to characterize EVs. For this tunable resistive pulse sensing (tRPS), nanoparticle tracking analysis (NTA) and high-resolution flowcytometry were used and studied. Once established that all of these methods have specific challenges and pitfalls, the systems were used to investigate the effect of glioblastoma EVs on cells of the innate immune system. In general it is shown that uptake of glioblastoma EVs is associated with a reduced immune function and increased tumor supportive function both in vitro and in vivo.