Therefore, we speculate that SLFN11 may shape an immunosuppressive/pro-tumor TME through regulation (especially inducing specific chemokine networks and immune checkpoint expression), which synergizes with its directly activated PI3K/AKT signaling pathway to jointly drive the aggressive progression and poor prognosis of ccRCC. The gene discussed is SLFN11; the disease is nonpapillary renal cell carcinoma.