Fig. 3: Exhausted CD8+ T cells are enriched in nccRCC TME.

A UMAP plot of three subsets of CD8+ T cells; B, C Dotplot of five top markers of each cell cluster; diameters of dots represent abundance, and color represents the expression level; D Differentiation trajectory of CD8+ T cells in nccRCC, with each color coded for pseudotime (left) and clusters (right); E Distribution of immune checkpoint expression in CD8+ T cells; F iTALK analysis revealed the interaction of immune checkpoints among the three clusters; the size of the arrow represent the relative expression level of the receptor (thick for high, small for low); the size of the line represent the relative expression level of the ligand (thick for high, small for low). G Volcano plot of upregulated and downregulated genes between clusters 3 and 2 (logFC > 0.9, p < 1e−5); upregulated genes are colored in red, and downregulated genes are colored in blue. H Heatmap of expression regulated by transcription factors estimated by SCENIC among the three clusters; upregulated TFs are colored in red, and downregulated TFs are colored in blue; I The distribution of EOMES and NFAT5 expression in CD8+ T cells, which participates in T cell dysfunction; J GSEA revealed pathways enriched in exhausted T cells. FDR < 0.05 was considered as significantly enriched. K, L The IHC analysis results of CD8+LAG3+ cells between para-Tumor and Tumor tissues. (random 20 fields and bar = 50 μm). M GSVA results of pathways enriched in exhausted T cells, and most cancer-associated pathways upregulated in exhausted T cells. Upregulated pathways are colored in red, and downregulated pathways are colored in blue.