CD4 and nonpapillary renal cell carcinoma: Dysfunctional or exhausted CD8 + cytotoxic T cells have been identified in ccRCC and the metastatic TME [32, 41] We found clusters of naïve CD4 (SELL, CCR7, CD4), naïve CD8 (SELL, CCR7, CD8A), T helper (CD4, RORC), Treg (FOXP3, CTLA4, IL2RA), NK1 (GZMB, FGFBP2, NKG7, KLRD1), NK2 (XCL1, XCL2, CMC1), proliferating T cells (TOP2A, MKI67), and three subtypes of CTLs, CTL-1 (CD8A, KLRG1, CMC1), CTL-2 (KLRB1, GZMK, IL7R), and CTL-3 (PDCD1, HAVCR2, IFNG, GZMK) (Fig. 3A, B and Additional file 2: Fig. S3A-C).