Abstract
Extracellular vesicle (EV) secretion is a ubiquitous cellular process with both physiologic and pathologic consequences. EVs are small lipid bilayer vesicles that encompass both microvesicles and exosomes and which are secreted by virtually all cells including cancer cells. In this review, we will focus on the roles of EVs in mediating the crosstalk between glioblastoma (GBM) cells and innate and adaptive immune cells and the potential impact on glioma progression. Glioma-derived EVs contain many bioactive cargoes that can broaden and amplify glioma cell mediated immunosuppressive functions and thereby contribute to shaping the tumor microenvironment. We will discuss evidence demonstrating that the low oxygen (hypoxia) in the GBM microenvironment, in addition to cell-intrinsic effects, can affect intercellular communication through EV release, raising the possibility that properties of the tumor core can more widely impact the tumor microenvironment. Recent advances in glioma-derived EV research have shown their importance not only as message carriers, but also as mediators of immune escape, with the capacity to reprogram tumor infiltrating immune cells. Exploring EV function in cancer-immune crosstalk is therefore becoming an important research area, opening up opportunities to develop EV monitoring for mechanistic studies as well as novel diagnostic glioma biomarker applications. However, robust and reproducible EV analysis is not always routinely established, whether in research or in clinical settings. Taking into account the current state of the art in EV studies, we will discuss the challenges and opportunities for extending the many exciting findings in basic research to a better interpretation of glioma and its response to current and future immunotherapies.
Highlights
Since the first comprehensive histomorphological description of glioblastoma multiforme (GBM) by Rudolf Virchow in the 19th century, it still remains a challenge to comprehensively describe its “multiforme” features, and to develop effective treatments
Downregulation of c-Myc by GBM Extracellular vesicle (EV)-derived miR-21 might promote a more global transition of the microglia/ macrophage phenotype that leads to the expression of a distinct transcriptional program rather than modulation of just one gene
The release of EVs from the hypoxic zones of GBM tumors was shown to induce M2 macrophage polarization in vitro, which subsequently promoted glioma proliferation, migration and invasion. This was demonstrated to be the result of EV-mediated delivery of miR1246 that polarized macrophages towards M2 by inhibiting NF-kB and activating the STAT3 pathway [56], which could serve as a polarization switch, as suggested for other cancers [57]
Summary
Since the first comprehensive histomorphological description of glioblastoma multiforme (GBM) by Rudolf Virchow in the 19th century, it still remains a challenge to comprehensively describe its “multiforme” features, and to develop effective treatments. EV internalization is not obligatory for EV functionality, since surface proteins can interact with receptors of the recipient cell plasma membrane that may lead to direct or indirect stimulation of intracellular signaling cascades All of these specific and nonspecific mechanisms of EV uptake and interactions represent the array of possibilities for EV-mediated intercellular communication that can induce epigenetic modifications in the recipient cells by transfer of bioactive molecules. The EVs of GBM cells carry different molecules than those of normal glial cells [16] These molecules include cancer effector molecules (e.g., mutant oncoproteins, oncogenic transcripts and oncomiRs) and can directly or indirectly support tumor progression and immune evasion [13, 17]. ROLE OF EVS IN THE CROSSTALK BETWEEN CANCER CELLS AND INNATE AND ADAPTIVE IMMUNE CELLS
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
