Extracellular vesicles from triple negative breast cancer promote pro-inflammatory macrophages associated with better clinical outcome
| Autor: | Mercedes Tkach, Jessie Thalmensi, Eleonora Timperi, Paul Gueguen, Nathalie Névo, Eleonora Grisard, Philemon Sirven, Federico Cocozza, Alizée Gouronnec, Lorena Martin-Jaular, Mabel Jouve, Fabien Delisle, Nicolas Manel, Derek C. Rookhuizen, Coralie L. Guerin, Vassili Soumelis, Emanuela Romano, Elodie Segura, Clotilde Théry |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Proceedings of the National Academy of Sciences. 119 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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