Here, we investigated the potential roles of new plasma biomarkers, including soluble PD-1 (sPD-1), sPD-L1, soluble PD-L2 (sPD-L2), and soluble LAG-3 (sLAG-3), as putative predictive biomarkers for determining the efficacy of IO combination therapy in advanced RCC. The gene discussed is SPDL1; the disease is renal cell carcinoma.