We analyzed 592 tumors collected from advanced ccRCC patients enrolled in prospective clinical trials (CheckMate 009, CheckMate 010, CheckMate 025) of treatment with PD-1 blockade...Our analysis revealed that CD8+ T cell infiltrated tumors are depleted of clinically favorable PBRM1 mutations (p = 0.013) and enriched for unfavorable chromosomal losses of 9p21.3 (p < 0.001) when compared to non-infiltrated tumors. When found within infiltrated tumors, del(9p21.3) was associated with worse CB rate (36% (9/25) for del(9p21.3) vs. 88% (7/8) for wildtype at that locus, p = 0.017) and worse survival (HR = 2.38, p = 0.01 for PFS; HR = 2.44, p = 0.01 for OS) with PD-1 blockade.