Here, we show that PD-1 is secreted in an exosomal form by activated T cells and can remotely interact with either cell surface or exosomal programmed death-ligand 1 (PD-L1), induce PD-L1 internalization via clathrin-mediated endocytosis, and thereby prevent subsequent cellular PD-L1: PD-1 interaction, restoring tumor surveillance through attenuating PD-L1-induced suppression of tumor-specific cytotoxic T cell activity. The gene discussed is CD274; the disease is neoplasm.