Analysis of more than 19,000 single CAF-S1 fibroblasts from breast cancer identified 8 CAF-S1 clusters. 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 Tregs, which, in turn, increases CAF-S1 cluster 3/TGFβ-myCAF cellular content. Here, TGFB1 is linked to breast carcinoma.