Single-Cell Analysis Reveals Fibroblast Clusters Linked to Immunotherapy Resistance in Cancer

Abstract A subset of cancer-associated fibroblasts (FAP+/CAF-S1) mediates immunosuppression in breast cancers, but its heterogeneity and its impact on immunotherapy response remain unknown. Here, we identify 8 CAF-S1 clusters by analyzing more than 19,000 single CAF-S1 fibroblasts from breast cancer. We validate the five most abundant clusters by flow cytometry and in silico analyses in other cancer types, highlighting their relevance. Myofibroblasts from clusters 0 and 3, characterized by extracellular matrix proteins and TGFβ signaling, respectively, are indicative of primary resistance to immunotherapies. Cluster 0/ecm-myCAF upregulates PD-1 and CTLA4 protein levels in regulatory T lymphocytes (Tregs),…

• NG
  National Geographic Society

  Award: ANR-10-INBS-09-08
• AN
  Agence Nationale de la Recherche

  Award: ANR-19-P3IA-0001
• IN
  Institut National de la Santé et de la Recherche Médicale

  Award: PC201317
• IN
  Institut National Du Cancer

  Awards: INCa-DGOS-Inserm-12554, CaLYS INCa-11692, INCa-11692, INCa-DGOS-9963