Extended Data Fig. 7: Genomic and transcriptomic characterization of the tLHP signature.
a, Heatmap showing tLHP expression in paired untreated and post-treatment samples. Rows represent individual patients and are hierarchically clustered by complete method. For multiple samples per treatment group, mean tLHP is displayed. b, Boxplots showing tLHP expression in paired untreated and post-treatment samples. P value as calculated with Kruskal-Wallis test. N numbers represent individual samples. c, Violinplots showing tLHP expression in treatment-naïve vs. post-VEGFR-TKI treated samples. Two-sided p-value as calculated by Mann-Whitney U test. d-f, Boxplots showing log10(TMB + 1) in TCGA-KIRC (d), Javelin101 (e) and IMmotion150 (f), by tLHP signature (dichotomized by optimal statistical cutoff). Two-sided p-value by Mann-Whitney U test. N numbers represent independent samples. g-i, Heatmap showing gene mutation status by sample in TCGA-KIRC (g), Javelin101 (h) and IMmotion150 (i). P values by Fisher’s Exact test are FDR-corrected. j, Boxplot showing TCR richness by tLHP signature (dichotomized by optimal statistical cutoff). Two-sided p-value as calculated by Mann-Whitney U test. N numbers represent individual samples. k, l, Dotplots showing correlation of CIBERSORTx cell types with tLHP signature in Leuven RWD cohort (k) and TCGA-KIRC (l) (Pearson or Spearman correlation depending on normality of cell type estimates. Two-sided p-values are FDR-corrected). m-q, Violinplot showing expression of tLHP signature by responder status for dendritic cells (m), monocytes (n), tumour cell type 2 (o), tumour cell type 1 (p) and regulatory T cells (q). N numbers represent independent cells. Two-sided p-values were calculated by Kolmogorov-Smirnov test. Effect sizes by Cohen’s D. r, Violin plot showing expression of tLHP signature per cell type (n = 152876 independent cells). s-u, Violinplot showing expression of tLHP signature in cells from untreated vs. ICB-treated patients, for all cells (s), TAM (t) and CD8+ T cells (u). N numbers represent independent cells. Two-sided p-values were calculated by Kolmogorov-Smirnov test, effect sizes by Cohen’s D. For all boxplots in this figure, boxes represent median (centre) and first/third quartile (bottom and top, resp.) values; whiskers show most extreme values within 1,5x interquartile range (IQR). Outliers extending beyond 1.5x IQR above/below the median are plotted individually.
