Co-stimulatory molecules such as CD28 and B7 mediate T cell activation, while co-inhibitory molecules including PD-1, CTLA-4, PD-L1, and PD-L2, which are known as “immune checkpoints”, function as T cell brakes.501,502 To date, the most well-studied immune checkpoints are CTLA-4, PD-1, and PD-L1, the blockade of which has shown promising effects against various cancers through reinvigorating antitumor immunity.503–508. This evidence concerns the gene CTLA4 and cancer.