Highlights d Distinct CD8 + T cell phenotypes are enriched after immune checkpoint blockade (ICB) d Immune checkpoint ligands are upregulated in macrophages and tumor cells after ICB d Two cancer cell subpopulations are conserved across heterogeneous RCC tumors d Cancer cell programs drive distinct immune interactions and predict patient outcomes

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Highlights d Molecular and clinical hallmarks of tRCC are defined via analysis of 152 samples d tRCC genomic alterations are rare aside from MiT/TFE fusions and 9p21.3 deletions d tRCCs display increased NRF2 pathway activation compared with other RCC subtypes d Immunotherapy may be active in some tRCCs