Extracellular vesicles: biogenesis mechanism and impacts on tumor immune microenvironment

Extracellular vesicles (EVs) are heterogeneous populations of membrane-bound particles released from almost all cell types in an organism and play pivotal roles in cell-cell communication. EVs carry nucleic acids, proteins, metabolites and other bioactive substances, which are taken by the recipient cells to alter cell physiology and functions. The cargo landscapes of EVs are influenced by the cell contexts and the biogenesis mechanisms of EVs, in which certain molecules govern both biogenesis and cargo sorting. In this review, we discuss the biogenesis and secretion mechanisms of various types of EVs, including several atypical EVs. In addition, given that the tumor immune microenvironment (TIME) is intricately controlled by the communication between tumor cells and various immune cells, we summarize the latest update about how tumor-derived EVs influence the phenotypes of various immune cells in tumor microenvironment for tumor immune evasion, and, conversely, how EVs secreted from immune cells in TIME control the malignancies of tumor cells. In particular, we discuss the roles of several atypical EVs in regulating TIME. Lastly, we highlight the advantages of utilizing EVs as liquid biopsies for cancer diagnosis, the application and challenge of EVs in different anti-tumor therapies, and the recent clinical trials that exploit EVs as drug carriers. As the continuous advances in our understanding of the complex biogenesis mechanisms and the pleiotropic actions of EVs in TIME as well as the technology improvements in harnessing EVs' clinical benefits, we can expect to further unlock the biomedical potential of EVs in cancer and other diseases.