The anti-CTLA-4 mAb Ipilimumab was the Food and Drug Administration (FDA) approved checkpoint inhibitor (iCPI) followed by approval of Pembrolizumab, Nivolumab, and Cemiplimab directed against PD-1, in 2014, 2016, or 2018, respectively, for non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC), bladder cancer and/or squamous cell skin cancer and the anti-PD-L1 mAbs Durvalumab, Atezolizumab, and Avelumab in 2017 after promising results in NSCLC, urothelial carcinoma and Merkel cell carcinoma (1–3). Here, CD274 is linked to renal cell carcinoma.