Fig. 4: Spatial deconvolution of TNBC molecular subtypes.

a Three levels of gene expression data: RNA sequencing from bulk tumors, ST global pseudobulk (captured from all ST spots), and ST tumor (green) and stroma (pink) pseudobulks (or compartments). b Contribution of tumor and stroma compartments to the TNBC molecular subtypes (N = 94). The alluvial plot shows the distribution of TNBC subtypes from ST global, tumor, and stroma pseudobulks, along with the spatial immunophenotypes (TIME classification). c Molecular and cellular characterization of tumor (top) and stroma (bottom) compartments across TNBC subtypes (N = 94). The most relevant and significant molecular and cellular features, including single gene expression, gene signatures, and xCell enrichment, are illustrated. FDRs are based on the Wilcoxon rank-sum test. FDR < 0.05 shown with dark-bordered dots; blue = negative association, red = positive association. Full effect sizes (by logistic regression) and FDRs are in Supplementary Fig. 3a, b. d Examples of the M subtype associated with either M (left) or MSL (right) stroma. Morphological regression shows the spatial distribution of tumor (green) and stroma (pink) signals. TNBC molecular classification is projected at the ST spot level. e Heatmap of molecular and cellular features characterizing the M subtype with M (left) (N = 11) or MSL (right) (N = 16) stroma (FDR < 0.05). f Kaplan–Meier plot of DRFS in patients with M subtype and either MSL or M stroma (N = 26). P value obtained using the permutation version of the log-rank test. Source data are provided as a Source Data file. Figure 4a was partly generated using Servier Medical Art, provided by Servier (https://smart.servier.com/), licensed under Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/). BL basal-like, FDR false-discovery rate, CAF cancer-associated fibroblast, DRFS distant relapse-free survival, EMT epithelial-mesenchymal transition, FI full inflamed, GGI genomic grade index, ID immune desert, IFNγ-iCAF interferon gamma signaling pathway cancer-associated fibroblast S1, IM immunomodulatory, IL-iCAF IL pathway inflammatory cancer-associated fibroblast S1, LAR luminal androgen receptor, M mesenchymal, MR margin restricted, MSL mesenchymal stem-like, PB pseudobulk, SR stroma restricted, ST spatial transcriptomics, TAM tumor associated macrophages, TIME Tumor Immune Micro-Environment, TLS tertiary lymphoid structure, Tregs regulatory T cells, Trm tissue-resident memory T cell.