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Single-cell analysis reveals fibroblast clusters linked to immunotherapy resistance in cancer

A subset of Cancer-Associated Fibroblasts (CAF-S1) mediates immunosuppression in breast cancers (BC), but its heterogeneity and its impact on immunotherapy response remain unknown. Here, we identify 8 CAF-S1 clusters by analyzing more than 18000 single CAF-S1 fibroblasts from BC. We validate the 5 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 extra-cellular matrix proteins and TGF signaling respectively, are indicative of primary resistance to immunotherapies. Cluster 0 up-regulates PD-1 and CTLA-4 protein levels in regulatory T lymphocytes (Tregs), which in turn increases CAF-S1 cluster 3 cellular content. Thus, our study highlights a positive feedback loop between specific CAF-S1 clusters and Tregs and uncovers their role in immunotherapy resistance.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001006163 Illumina HiSeq 2500 Illumina NovaSeq 6000 8
Publications Citations
Single-Cell Analysis Reveals Fibroblast Clusters Linked to Immunotherapy Resistance in Cancer.
Cancer Discov 10: 2020 1330-1351
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