Only few reports demonstrate that the activation of P2Rs on immune cells induces the release of: (i) EVs containing IL-1β and IL-18, exerting a pro-inflammatory action, favor tumor progression at the expense of an effective immune response; (ii) EVs presenting P2Rs on their surfaces which activation, by extracellular ATP, can lead to the release of IL-1β, IL-18 and ATP itself (27). This evidence concerns the gene IL18 and neoplasm.