CTLA-4 interacts with CD80 and CD861–3 to ensure proper function of regulatory T cells4 and protect host against autoinflammatory diseases.5–8 Anti-CTLA-4 monoclonal antibodies (mAbs) have demonstrated strong and broad cancer immunotherapeutic effects (CITE) in a variety of preclinical models9–11 and are used clinically both as monotherapy12,13 and as part of combination therapy with Nivolumab.14,15 However, compared with anti-PD-1/PD-L1 antibodies, CTLA-4-targeting in cancer patients has been less successful. This evidence concerns the gene CD274 and cancer.