Tumor-Derived Extracellular Vesicles: Multifunctional Entities in the Tumor Microenvironment.

Tumor cells release extracellular vesicles (EVs) that can function as mediators of intercellular communication in the tumor microenvironment. EVs contain a host of bioactive cargo, including membrane, cytosolic, and nuclear proteins, in addition to noncoding RNAs, other RNA types, and double-stranded DNA fragments. These shed vesicles may deposit paracrine information and can also be taken up by stromal cells, causing the recipient cells to undergo phenotypic changes that profoundly impact diverse facets of cancer progression. For example, this unique form of cellular cross talk helps condition the premetastatic niche, facilitates evasion of the immune response, and promotes invasive and metastatic activity. These findings, coupled with those demonstrating that the number and content of EVs produced by tumors can vary depending on their tumor of origin, disease stage, or response to therapy, have raised the exciting possibility that EVs can be used for risk stratification, diagnostic, and even prognostic purposes. We summarize recent developments and the current knowledge on EV cargoes, their impact on disease progression, and implementation of EV-based liquid biopsies as tumor biomarkers. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease , Volume 18 is January 2023. Please see https://www.annualreviews.org/page/journal/pubdates for revised estimates.