Single-cell profiling reveals a novel CAF subpopulation linking stromal heterogeneity to immune suppression in breast cancer subtypes - PubMed
3 hours ago
- #Cancer-Associated Fibroblasts
- #Breast Cancer
- #Immune Suppression
- Single-cell RNA-seq identified three conserved stromal populations (iCAFs, myCAFs, pericytes) and a novel metabolic stressed CAF (msCAF) subset in breast cancer.
- msCAFs showed transcriptional programs linked to antigen presentation, stress response, glycolysis, and ECM remodeling, and their abundance inversely correlated with T-cell infiltration and function in a subtype-specific manner.
- TNBC tumors were enriched with msCAFs in immune-infiltrated but functionally constrained microenvironments, while Luminal A tumors had weaker immune infiltration and heterogeneous CAF-immune associations.
- msCAFs had a conserved gene signature (HLA-A, HLA-C, IL32, EMP3) and subtype-specific genes related to T-cell exhaustion, with distinct prognostic markers for Luminal A and TNBC subtypes.
- Several msCAF genes predicted chemotherapy response, suggesting their utility as biomarkers for treatment stratification and highlighting msCAFs as targets to enhance immunotherapy and personalize breast cancer treatment.