Fig 2: Schematic illustration of the molecular mechanism by which TN-BCSC-derived CHI3L1 promotes immune escape of TNBC via the MAF/CTLA4 axis. TNBC mainly contains 8 cell subsets, among which TN-BCSCs exist in the epithelial cell subgroup. As a characteristic gene expressed in TN-BCSCs, CHI3L1 is related to TNBC cell stemness. It upregulates the expression of CTLA4 in T cells through MAF, thereby inhibiting the cytotoxicity of CD8+ T cells and producing immunosuppression. CTLA4+ T cells promote the stemness phenotype of TNBC cells by secreting S100A4 through positive feedback

Fig 3: Fibroblasts released S100A4 to promote PD-L1 expression in epithelial cells. (A) Bulk RNA results demonstrate that S100A4 significantly rises after neoadjuvant therapy in the nMPR group. (B) IHC results of a-SMA (the fibroblast marker protein) and S100A4. The a-SMA and S100A4 show co-localization. (C) Western blot reveals the expression of PD-L1 protein under different stimulations. (D) Both S100A4 and the fibroblast culture medium (CAF-CM) can significantly enhance the expression of PD-L1, but there is no significant difference between S100A4 and CAF-CM.

Fig 4: S100A4 is associated with poor efficacy and tumor progression. (A) The various meta-programs of epithelial cells. (B) The various meta-programs of fibroblasts. (C) GO annotation of MPs in epithelial cells and fibroblasts. (D) 3CA database annotation of MPs in epithelial cells and fibroblasts. (E) The proportions of various MPs in epithelial cells and fibroblasts. (F) The correlation between MPs in epithelial cells and fibroblasts. (G) MPs related to tumor progression in fibroblasts. (H) DEGs of epithelial cells/fibroblasts related to fibroblast MP5, as well as the key protein-protein interaction network. (I) The expression of key genes in fibroblasts, among which S100A4 has the highest expression level.