CTLA-4 is downregulated during the early activation and maturation of T cells in lymph nodes, while PD-1 predominantly regulates their functional responses at the tumor site.664–666 Various immune checkpoints manifest distinct spatiotemporal effects, as illustrated by CTLA-4 and PD-1/PD-L1.667 CTLA-4 primarily governs T cell activation in lymph nodes and impedes DCs activity through Treg cells. The gene discussed is CD274; the disease is neoplasm.