Deciphering the spatial landscape and plasticity of immunosuppressive fibroblasts in breast cancer.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
01 Apr 2024
01 Apr 2024
Historique:
received:
01
08
2023
accepted:
19
03
2024
medline:
2
4
2024
pubmed:
2
4
2024
entrez:
1
4
2024
Statut:
epublish
Résumé
Although heterogeneity of FAP+ Cancer-Associated Fibroblasts (CAF) has been described in breast cancer, their plasticity and spatial distribution remain poorly understood. Here, we analyze trajectory inference, deconvolute spatial transcriptomics at single-cell level and perform functional assays to generate a high-resolution integrated map of breast cancer (BC), with a focus on inflammatory and myofibroblastic (iCAF/myCAF) FAP+ CAF clusters. We identify 10 spatially-organized FAP+ CAF-related cellular niches, called EcoCellTypes, which are differentially localized within tumors. Consistent with their spatial organization, cancer cells drive the transition of detoxification-associated iCAF (Detox-iCAF) towards immunosuppressive extracellular matrix (ECM)-producing myCAF (ECM-myCAF) via a DPP4- and YAP-dependent mechanism. In turn, ECM-myCAF polarize TREM2+ macrophages, regulatory NK and T cells to induce immunosuppressive EcoCellTypes, while Detox-iCAF are associated with FOLR2+ macrophages in an immuno-protective EcoCellType. FAP+ CAF subpopulations accumulate differently according to the invasive BC status and predict invasive recurrence of ductal carcinoma in situ (DCIS), which could help in identifying low-risk DCIS patients eligible for therapeutic de-escalation.
Identifiants
pubmed: 38561380
doi: 10.1038/s41467-024-47068-z
pii: 10.1038/s41467-024-47068-z
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2806Subventions
Organisme : Institut National Du Cancer (French National Cancer Institute)
ID : INCa-11692
Organisme : Institut National Du Cancer (French National Cancer Institute)
ID : INCa-16101
Informations de copyright
© 2024. The Author(s).
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