Deciphering the spatial landscape and plasticity of immunosuppressive fibroblasts in breast cancer.
Nat Commun
; 15(1): 2806, 2024 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-38561380
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.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Carcinoma Intraductal não Infiltrante
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Receptor 2 de Folato
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Fibroblastos Associados a Câncer
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article