The clinical efficacy of PD-1/L1 blocking antibodies was first observed against tumors with high PD-L1 expression, including melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC).42,106,107 The PD-1 blocking antibody nivolumab (Opdivo) was approved in 2015 for advanced squamous cell lung cancer treatment, marking the first clinical application of anti-PD-1 therapy. Here, CD274 is linked to hereditary clear cell renal cell carcinoma.