Multi-functional extracellular vesicles: Potentials in cancer immunotherapy

Cancer immunotherapy (CIT) has revolutionized cancer treatment. However, the application of CIT is limited by low response rates and significant individual differences owing to a deficit in 1) immune recognition and 2) immune effector function. Extracellular vesicles (EVs) are cell-derived lipid bilayer-enclosed vesicles that mediate intercellular communication. The specific structure and content of EVs allows for multi-functional modulation of tumor immunity. Given their high biocompatibility, homologous targeting, and permeability across biological barriers, EVs have been evaluated as ideal carriers for promoting the efficacy and specificity of CIT. Herein, we first discuss the role of EVs in regulating tumor immunity and focus on the advantages of using EVs as a therapeutic tool for cancer treatment from a clinical perspective. Further, we outline the current progress in the development of biohybrid EVs for CIT and multi-functional EV-based strategies for overcoming the deficits in tumor immunity. Finally, we discuss the challenges associated with EV-based CIT and future perspectives in the context of ongoing clinical trials involving EV-based therapies, thus offering valuable insights into the future of multi-functional EVs in CIT.