Many hypotheses underlie this contra-intuitive prognosis on the impact of CD8 in ccRCC: amongst them, it was demonstrated that CD8 TILs in ccRCC are mostly exhausted with frequent co-expression of PD-1 and lymphocyte-activation gene 3 (LAG-3), due to a lack of antigen presentation by dysfunctional/immature dendritic cells[62]. This evidence concerns the gene CD8A and nonpapillary renal cell carcinoma.