Fig. 5: Cell types and states associated with discordance and immunotherapy response.

The heatmaps show the significantly different cell types/states in patients that have one or two (groups 1-2) prognostic classifiers that are discordant with patients that are unanimously classified (group 0) as either high (a) or low (b) risk as the reference group. The legends refer to the row metadata for group (cell type), −log₁₀ (FDR) with red values denoting significant results from a Kruskal-Wallis test (FDR < 0.05), results from Dunn’s multiple comparison tests for each pairwise comparison (gray box, FDR < 0.05; white box, FDR > 0.05; note that post hoc comparisons are depicted even if the Kruskal-Wallis test was not significant), and the cube root transformed cell type/state abundances. The data in the high (a) and low (b) risk heatmaps are the same as presented in Supplementary Fig. 12, but the labels for low risk have been changed from 5, 4, and 3 to 0, 1, and 2. Box and whisker plots illustrate the exemplary cell types/states that are differentially expressed when comparing high- and low-risk samples (top panel graphs) as well as patients that have 1 or 2 discordant classifiers for high risk relative to those who have unanimous agreement (bottom panels). Cell types/states include CD8 T cells – Exhausted/effector memory (SO3) (c), CD4 T cells – Exhausted / effector memory / Treg (SO1) (d), Dendritic cells – Mature immunogenic (S03) (e), Monocytes/Macrophages – M2-like proliferative (S07) (f), Epithelial cells – Pro-inflammatory (SO4) (g), Fibroblasts – Pro-migratory-like (SO8) (h). Statistical comparisons are only shown for bottom panels and were performed using the Kruskal-Wallis test (n = 575). *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. Boxes denote the interquartile range with the line plotted as the median, whiskers show the 5 and 95 percentiles, and dots are individual samples outside this range. (i) Bar graphs show the percentage of patients (n = 40) who achieved pathological complete response following neoadjuvant treatment with paclitaxel combined with pembrolizumab in the I-SPY2 trial stratified by biomarker subgroups. Source data are provided as a Source Data file.