Fig. 5: Cell–cell interaction analysis reveals potential therapeutic targets in ccRCC.

a Overview of potential ligand-receptor interactions of cell subpopulations. b Bubble heatmap showing expression of ligand (tumor cells and stromal cell subsets) and receptor (immune cell subsets) pairs in different stromal and immune subsets. Dot size indicates expression ratio, color represents average gene expression. Significance of ligand-receptor pair is determined by permutation test, gene differential expression analysis and specific cellular expression (Methods). c The predicted interactions between CD70 and CD27. d Violin plot showing CD27 expression in CTL-1 and Tregs. e CD27 and CD70 expression in TCGA KIRC data are shown as boxplot. Statistics are accessed with a two-side Wilcoxon rank-sum test (CD27 ****p < 2e-16; CD70 ****p < 2e-16. Sample size: Tumor n = 533, Normal n = 53). Boxplots include center line, median; box limits, upper and lower quartiles; and whiskers are highest and lowest values no greater than 1.5× interquartile range. f Correlation of CD70–CD27 (tumor cells-CTL-1) average expression and CTL-1 exhaustion score is shown as scatter plot. Pearson linear correlation estimate, and p-values are shown. The error band indicates 95% confidence interval. g Flow cytometric analysis of CD27 expression on PDCD1 + CD8 + T cells from Tumor and paired adjacent normal tissue. (n = 4 per group). Statistics are accessed with paired two-side t-test (**p = 0.0031). h Spatial feature plots showing CA9, CD70, and CD27 expression in ccRCC patient. Tumor spots are marked by CA9 expression. i CXCL9 and CXCL10 expression in TCGA KIRC data are shown as boxplot. Statistics are accessed with a two-side Wilcoxon rank-sum test (CXCL9 ****p < 2e-16; CXCL10 **** p < 2e-16. Sample size: Tumor n = 533, Normal n = 53). Boxplots include center line, median; box limits, upper and lower quartiles; and whiskers are highest and lowest values no greater than 1.5× interquartile range. Source data are provided as a Source Data file.