A game of hide-and-seek: how extracellular vesicles evade the immune system

Extracellular vesicles (EVs) are heterogeneously sized, cell-derived nanoparticles operating as proficient mediators of intercellular communication. They are produced by normal as well as diseased cells and carry a variety of cargo. While the molecular details of EV biology have been worked out over the past two decades, one question that continues to intrigue many is how are EVs able to evade the phagocytic immune cells while also being effectively internalized by the target cell or tissue. While some of the components that facilitate this process have started to be identified, many mechanisms are yet to be dissected. This review summarises some of the key mechanisms that cancer cell-derived and viral infected cell-derived EVs utilize to evade the immune system. It will discuss the diverse cloaking mechanisms, in the form of membrane proteins and cargo content that these EVs utilize to enhance pathogenesis. Further, it will highlight the different strategies that have been used to design EVs to escape the immune system, thereby increasing their circulation time with no major toxic effects in vivo. An understanding of the potential EV components that allow better immune evasion can be used to bioengineer EVs with better circulation times for therapeutic purposes.