As ccRCC advances, CD8 + T cells increasingly express inhibitory checkpoints like programmed cell death protein 1 (PD-1), TIM-3, and lymphocyte—activation gene 3 (LAG3), and TFs thymocyte selection—associated high mobility group box protein (TOX) and EOMES, which are associated with terminal exhaustion [225, 254]. This evidence concerns the gene PDCD1 and nonpapillary renal cell carcinoma.