SMPD3 and cancer: Likewise, Poggio et al. have found that castration-resistant cancer-secreted small vesicles carrying PD-L1 significantly impair T lymphocyte activation and favor tumor progression in vivo; notably, the injection of EV-deficient PCa cells, obtained by silencing two genes involved in vesicular biogenesis (Rab27a and nSMase 2), together with an anti-PD-L1 antibody has been associated with a remarkable decrease in cancer growth and a parallel increase in mouse survival [46].