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

Abstract

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.