In contrast, a recent study demonstrated that M2-type macrophage-derived extracellular vesicles (EVs) target and inhibit OTUD2 by secreting miR-21-5p, which leads to activation of the YAP/β-catenin pathway and subsequent CD8+ T cell depletion, whereas OTUD2 overexpression enhances the CD8+ T-cells by inhibiting the YAP/β-catenin pathway’s antitumor effects, thereby inhibiting HCC [50] (Fig. 2). The gene discussed is CD8A; the disease is hepatocellular carcinoma.