In the present work, we have employed ex vivo CRISPR/Cas9-mediated gene ablation of Nr2f6 prior to therapeutic adoptive transfer, in order to determine whether acute inhibition of NR2F6 gene function indeed enables improved therapeutic anti-cancer activity by the approved PD-L1 or CTLA-4 immune checkpoint therapy in vivo and thus could be a useful dual strategy to elicit meaningful and host-protective tumor immunity. This evidence concerns the gene CD274 and cancer.