In ccRCC, high MAEL expression was associated with VEGFR/mTOR activation and an anti-inflammatory TIME, which can explain the high sensitivities to VEGFR/PI3K-AKT-mTOR inhibitors and the poor benefit from ICI-based therapies over VEGFR/mTOR inhibitors. Here, AKT1 is linked to nonpapillary renal cell carcinoma.