Mechanically, we demonstrated that NFAT1 increased the PD-L1 expression level by initiating the transcription of TNF, and the dysregulated Phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase (AKT)/ glycogen synthase kinase 3 beta (GSK-3β) signaling pathway in sunitinib-resistant RCC cells stabilizing NFAT1 via inhibiting the FBW7 function. The gene discussed is NFATC2; the disease is renal cell carcinoma.