Fig. 5. Estimated abundance of CD8+ T cells along the exhaustion trajectory in skin melanoma.
a, UMAP embedding of melanoma reference scRNA-seq data, where cells are colored according to their cell types (blue, CD8+ T cells). CAFs, cancer-associated fibroblasts; NK cells, natural killer cells. b, Expression pattern of the marker genes along the exhaustion trajectory. The lines represent the fitted curve using the LOESS, and the shaded area indicates the 95% CI. c, Estimated cell-state abundances of CD8+ T cells in patients stratified into tertiles by TCR expansion level in TCGA data (n = 430). The x axis represents the exhaustion trajectory, from the naive state (left) to the exhausted state (right). The curved line shows mean estimated cell-state abundance across individuals. The P value was computed using MANOVA-Pro and was capped by the number of permutations. d, Kaplan–Meier plot for overall survival between two groups of patients with melanoma stratified by the estimated abundance of CD8+ T cells in each tertile of the exhaustion state in TCGA data. The exhaustion-state tertiles are: time 1, the low-exhaustion state (0–33% of the exhaustion trajectory); time 2, the medium-exhaustion state (33–66% of the exhaustion trajectory); time 3, the high-exhaustion state (66–100% of the exhaustion trajectory). The shaded area represents the 95% CI of the fitted Kaplan–Meier curves. The P values were computed using a two-sided long-rank test. e, Boxplot of estimated cell-state abundance of CD8+ T cells in the patients with melanoma who did not respond to anti-PD-1 ICB (n = 36) versus the responders (n = 34) in each of the exhaustion-state tertiles. Each point represents one patient, color-coded based on their response to ICB. The P value was computed using a two-sided Wilcoxon test. The box indicates the IQR, the line within the box represents the median value and the whiskers extend to data points within 1.5 times the IQR.