Liver cells and PBMC secrete Tumor-suppressive Plasma Extracellular Vesicles in Melanoma patients

Summary Before and after surgery melanoma patients harbor elevated levels of extracellular vesicles in plasma (pEV), but their cellular origin is obscure. Here we suggest that these pEV are secreted in part by tumor cells, but particularly by liver and peripheral blood mononuclear cells (PBMC), which strongly suppressed tumor cell activity. As the cellular origin of pEV is difficult to determine, we mimicked the interaction of tumor cells with liver cells and PBMC in vitro, and compared newly secreted EV-associated miRNAs and protein factors with those detected in melanoma patient’s pEV. The results identified factors that could be associated either with tumor cell activity or the counteracting immune system and liver cells. Notably, the presence/absence of these factors correlated with the clinical stage and tumor relapse. Our study provides new insights into the innate immune defense against tumor cells and implies that residual tumor cells may be more active than previously thought. Summary blurb Plasma extracellular vesicles (pEV) in melanoma patients are a mix of cancer cell-suppressive vesicles from liver cells and PBMC, but derive also from residual cancer cells.