Thus, our data reveal a novel role for the FBW7/NFAT1 axis in the response of RCC to TKIs and ICIs therapy, and the treatment to target FBW7/NFAT1 axis might be a novel therapy strategy to enhanced the anti-tumor effect of PD-1 antibody, especially for sunitinib-resistant RCC patients. Here, NFATC2 is linked to renal cell carcinoma.