Extracellular vesicles role in radio(nuclide)therapy

Abstract

Conventional radiation therapy can restore the ability of cells to undergo immunogenic cell death. Recent preclinical studies suggest that targeted radionuclide therapy, which delivers radiation to tumors at a continuous low dose rate, also stimulates the immune system and offers a promising approach for overcoming resistance to immune checkpoint inhibitors. In this context, we examined the growing body of preclinical and clinical findings showing that the immune system can be activated by the release of extracellular vesicles from irradiated cells, contributing to the antitumor immunity.

Keywords: bystander; exosomes; microvesicles; radioimmunotherapy; radiopharmaceuticals.

Fig. 1

EV characteristics, mechanisms of secretion and structure. Different EV subtypes are depicted as well as their size range and other co-isolated particles (upper panel). Selected examples of the crosstalk between the intracellular molecular machineries involved in the biogenesis and secretion of microvesicles formed at the plasma membrane and exosomes formed in late endosomal multivesicular body (MVB) (middle panel). Studies on EVs structure have shown that their cargo can include different molecules, such as proteins, lipids and nucleic acids (lower panel). The cargo content can vary significantly depending on the cell type and the conditions of EV production. The specific composition of these vesicles influences their fate and function, highlighting the importance of mechanisms that selectively sort their contents. Notably, EVs from different cell types carry distinct sets of cell type-specific proteins that contribute to their unique roles and functions. Despite their different modes of formation, exosomes and microvesicles have similar appearance, overlapping sizes and often similar composition. This makes difficult to determine their origin once they are isolated from the extracellular environment or biological fluids.