The Mediating Role of Exosomes in Response to Radiotherapy

Exosomes are small extracellular vesicles produced by almost all cells. They play a key role in intercellular communication by transferring biologically active molecules from the cell of origin to the recipient cells. Being mediators of cell to cell communication, they activate different signaling pathways which leads to affection of receipient cell activity. Radiotherapy, as a kind of environmental stress disrupt the homeostasis of the tumor microenvironment and it has been shown that exposing to ionizing radiation increase exosome secretion and influense on their molecular cargo loading. Exosomes from irradiated cells play a key role in transferring resistance traits to neighboring or distant cells. By modulating DNA repair, survival pathways, oxidative stress, immune responses, and apoptosis, they contribute to an overall increase in radioresistance in recipient cells and promote tumor survival. Therefore, exosomes hold great promise for clinical application in reducing radioresistance.Furthermore, radiotherapy can induce radiation induced bystander effect, not only on nonirradiated tumor cells leading to tumor cell death but also on normal cells and tissue leading to radiation injury. Exosomes can transmit the radiation induced bystander effect (RIBE) by using miRNAs as effectors, so they may be a potential therapeutic target to eradicate tumor cells outside from treated volume and protect nonirradiated normal cells.Understanding the complex role of exosomes in radiotherapy helps developing novel strategies for overcoming radioresistance and improving treatment outcomes.