Recent studies suggest that when PD‐L1 on the surface of tumor cells is blocked by PD‐L1 antibody, tumor cells will cleverly repopulate the intracellular PD‐L1 to cell surface to maintain a homeostasis state and finally mediate immune resistance/invasion.[4, 5] Therefore, seeking potent alternatives to completely and permanently silence PD‐L1 expression of cancer cells would be a promising strategy to enhance ICB efficacy. The gene discussed is CD274; the disease is cancer.