Chen et al. designed tumor-targeting lipid NPs to deliver siRNA against the immune checkpoint ligand PD-L1 and immunostimulatory IL-2-encoding plasmid DNA, which reprogrammed the TME and synergized with a hepatoma vaccine by increasing tumor-infiltrating CD8+ T cells and the expression of IFN-γ and granzyme B, resulting in significantly improved antitumor efficacy compared with that of vaccine alone (Fig. 7). The gene discussed is CD8A; the disease is neoplasm.