Notably, whereas PD-1 had a broad expression both CD8+ and CD4+ T cell population, other inhibitory molecules, like TIM-3, CTLA-4, and 4-1BB (CD137) were expressed only by a few PD-1+ subsets, indicating that a pre-exhaustion status is also present in ccRCC (108). This evidence concerns the gene PDCD1 and nonpapillary renal cell carcinoma.