Effects of glioblastoma-derived extracellular vesicles on the functions of immune cells.

Abstract

Glioblastoma is the most aggressive variant of glioma, the tumor of glial origin which accounts for 80% of brain tumors. Glioblastoma is characterized by astoundingly poor prognosis for patients; a combination of surgery, chemo- and radiotherapy used for clinical treatment of glioblastoma almost inevitably results in rapid relapse and development of more aggressive and therapy resistant tumor. Recently, it was demonstrated that extracellular vesicles produced by glioblastoma (GBM-EVs) during apoptotic cell death can bind to surrounding cells and change their phenotype to more aggressive. GBM-EVs participate also in establishment of immune suppressive microenvironment that protects glioblastoma from antigen-specific recognition and killing by T cells. In this review, we collected present data concerning characterization of GBM-EVs and study of their effects on different populations of the immune cells (T cells, macrophages, dendritic cells, myeloid-derived suppressor cells). We aimed at critical analysis of experimental evidence in order to conclude whether glioblastoma-derived extracellular vesicles are a major factor in immune evasion of this deadly tumor. We summarized data concerning potential use of GBM-EVs for non-invasive diagnostics of glioblastoma. Finally, the applicability of approaches aimed at blocking of GBM-EVs production or their fusion with target cells for treatment of glioblastoma was analyzed.