Extracellular vesicles in tumor immunotherapy

Abstract As endogenous nanocarriers and mediators of cell-to-cell communication, extracellular vesicles (EVs) have been emerging as promising therapeutic agents to combat many diseases. Of the different categories of EVs, exosomes have gained particular prowess in therapeutic development due to valuable pharmacological properties. Exosomes are small membranous vesicles secreted from diverse types of cells, and upon their biogenesis, they inherit contents including proteins, DNA fragments, and RNAs from parental cells. The subsequent release of exosomes into the extracellular space plays an important role in intercellular communication by initiating signaling through inherited surface ligands and transferring cargo contents upon uptake. Tumor-derived exosomes have been shown to be critical for tumor metastasis, angiogenesis, and microenvironmental modulation through these processes. Moreover, given their abilities to modulate the immune system, exosomes have also become important candidates for immunotherapy. In this chapter, the biogenesis, physiological functions, and roles in immune modulation for exosomes are first introduced. Exosome-based cancer applications are then highlighted such as cancer vaccines, exosome as delivery vehicles of therapeutic cargos, and current clinical and translational research. Lastly, the future development of exosomes in immunotherapy is discussed.