PRF1 and neoplasm: Thus, Tadokoro et al. [58] showed that EVs secreted by cell lines of breast cancer are disrupted by perforin, a pore-forming protein liberated by CD8+ cytotoxic lymphocytes (CTLs), when activated by the known cytokine interferon-gamma (IFN-γ), whose release in vivo is generally stimulated by the tumor presence and aims at rejecting the tumor itself [59].