At the protein level, we used flow cytometry to validate the co-expression of dysfunction markers (for example, PD1, TOX, EOMES, CD39 and TIM3) with FAS, TRAF1 and 4-1BB in tumor-infiltrating CD8+ T cells in ccRCC patient samples that had also been analyzed by single-cell transcriptomic/epigenomic assays, as well as in an additional set of tumor samples (n = 9; Supplementary Table 1) (Fig. 4d and Extended Data Fig. 9a). Here, HAVCR2 is linked to nonpapillary renal cell carcinoma.