Pro-tumoral functions of tumor-associated macrophage EV-miRNA.

MicroRNAs (miRNAs) are central players in cancer biology. Their relevance in cancer development, progression and resistance to therapy has been further emphasized by the discovery that they are important cargo component of extracellular vesicles (EVs), which represent a prominent means of inter-cellular communication within the tumor microenvironment (TME). This review article focuses on the interaction between cancer cells and tumor-associated macrophages (TAMs) and in particular on the pro-tumoral phenotype elicited by EV-contained miRNAs released by TAMs and transferred to cancer cells. All main hallmarks of the malignant phenotype are affected by TAM-derived vesicular miRNAs, paving the road to the identification of such miRNAs as promising upcoming novel anti-cancer agents.

Diverse roles of EV-RNA in cancer progression.

Extracellular vesicles (EVs) have emerged as important players in all aspects of cancer biology. Their function is mediated by their cargo and surface molecules including proteins, lipids, sugars and nucleic acids. RNA in particular is a key mediator of EV function both in normal and cancer cells. This statement is supported by several lines of evidence. First, cells do not always randomly load RNA in EVs, there seems to be a specific manner in which cells populate their EVs with certain RNA molecules. Moreover, cellular uptake of EV-RNA and the secondary compartmentalization of EV-RNA in recipient cells is widely reported, and these RNAs have an impact on all aspects of cancer growth and the anti-tumoral immune response. Additionally, EV-RNA seems to work through various mechanisms of action, highlighting the intricacies of EVs and their RNA cargo as prominent means of inter-cellular communication.

Professional killers: The role of extracellular vesicles in the reciprocal interactions between natural killer, CD8+ cytotoxic T-cells and tumour cells.

Extracellular vesicles (EVs) mediate the cross-talk between cancer cells and the cells of the surrounding Tumour Microenvironment (TME). Professional killer cells include Natural Killer (NK) cells and CD8+ Cytotoxic T-lymphocytes (CTLs), which represent some of the most effective immune defense mechanisms against cancer cells. Recent evidence supports the role of EVs released by NK cells and CTLs in killing cancer cells, paving the road to a possible therapeutic role for such EVs. This review article provides the state-of-the-art knowledge on the role of NK- and CTL-derived EVs as anticancer agents, focusing on the different functions of different sub-types of EVs. We also reviewed the current knowledge on the effects of cancer-derived EVs on NK cells and CTLs, identifying areas for future investigation in the emerging new field of EV-mediated immunotherapy of cancer.

Biological membranes in EV biogenesis, stability, uptake, and cargo transfer: an ISEV position paper arising from the ISEV membranes and EVs workshop.

Paracrine and endocrine roles have increasingly been ascribed to extracellular vesicles (EVs) generated by multicellular organisms. Central to the biogenesis, content, and function of EVs are their delimiting lipid bilayer membranes. To evaluate research progress on membranes and EVs, the International Society for Extracellular Vesicles (ISEV) conducted a workshop in March 2018 in Baltimore, Maryland, USA, bringing together key opinion leaders and hands-on researchers who were selected on the basis of submitted applications. The workshop was accompanied by two scientific surveys and covered four broad topics: EV biogenesis and release; EV uptake and fusion; technologies and strategies used to study EV membranes; and EV transfer and functional assays. In this ISEV position paper, we synthesize the results of the workshop and the related surveys to outline important outstanding questions about EV membranes and describe areas of consensus. The workshop discussions and survey responses reveal that while much progress has been made in the field, there are still several concepts that divide opinion. Good consensus exists in some areas, including particular aspects of EV biogenesis, uptake and downstream signalling. Areas with little to no consensus include EV storage and stability, as well as whether and how EVs fuse with target cells. Further research is needed in these key areas, as a better understanding of membrane biology will contribute substantially towards advancing the field of extracellular vesicles.