Bibliographic Details
| Title: |
Deciphering the spatial landscape and plasticity of immunosuppressive fibroblasts in breast cancer |
| Authors: |
Hugo Croizer, Rana Mhaidly, Yann Kieffer, Geraldine Gentric, Lounes Djerroudi, Renaud Leclere, Floriane Pelon, Catherine Robley, Mylene Bohec, Arnaud Meng, Didier Meseure, Emanuela Romano, Sylvain Baulande, Agathe Peltier, Anne Vincent-Salomon, Fatima Mechta-Grigoriou |
| Source: |
Nature Communications, Vol 15, Iss 1, Pp 1-28 (2024) |
| Publisher Information: |
Nature Portfolio, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Science |
| Subject Terms: |
Science |
| More Details: |
Abstract 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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2041-1723 |
| Relation: |
https://doaj.org/toc/2041-1723 |
| DOI: |
10.1038/s41467-024-47068-z |
| Access URL: |
https://doaj.org/article/73b3042cd19346fdaed2121d0b1ae858 |
| Accession Number: |
edsdoj.73b3042cd19346fdaed2121d0b1ae858 |
| Database: |
Directory of Open Access Journals |
