Accordingly, we discovered that a significant increase of circulating uPAR+ (urokinase-type Plasminogen Activator Receptor) EVs released from melanoma, CD8+ T-cells and dendritic cells correlated with unresponsiveness in a cohort of MM patients subsequently treated with nivolumab or pembrolizumab, further supporting the notion that EV-based biomarkers are powerful tool to predict innate resistance to ICI [25]. This evidence concerns the gene CD8A and Miyoshi myopathy.