Extracellular vesicles from triple negative breast cancer promote pro-inflammatory macrophages associated with better clinical outcome.
CSF-1
exosomes
extracellular vesicles
macrophages
triple-negative breast cancer
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
26 04 2022
26 04 2022
Historique:
entrez:
19
4
2022
pubmed:
20
4
2022
medline:
22
4
2022
Statut:
ppublish
Résumé
Tumor associated macrophages (TAMs), which differentiate from circulating monocytes, are pervasive across human cancers and comprise heterogeneous populations. The contribution of tumor-derived signals to TAM heterogeneity is not well understood. In particular, tumors release both soluble factors and extracellular vesicles (EVs), whose respective impact on TAM precursors may be different. Here, we show that triple negative breast cancer cells (TNBCs) release EVs and soluble molecules promoting monocyte differentiation toward distinct macrophage fates. EVs specifically promoted proinflammatory macrophages bearing an interferon response signature. The combination in TNBC EVs of surface CSF-1 promoting survival and cargoes promoting cGAS/STING or other activation pathways led to differentiation of this particular macrophage subset. Notably, macrophages expressing the EV-induced signature were found among patients’ TAMs. Furthermore, higher expression of this signature was associated with T cell infiltration and extended patient survival. Together, this data indicates that TNBC-released CSF-1-bearing EVs promote a tumor immune microenvironment associated with a better prognosis in TNBC patients.
Identifiants
pubmed: 35439048
doi: 10.1073/pnas.2107394119
pmc: PMC9169908
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2107394119Subventions
Organisme : NIDA NIH HHS
ID : R01 DA040385
Pays : United States
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