Extracellular vesicles from triple negative breast cancer promote pro-inflammatory macrophages associated with better clinical outcome
Menée à l'aide de lignées cellulaires ainsi que d'échantillons tumoraux et d'échantillons tissulaires adjacents issus de patientes atteintes d'un cancer du sein triple négatif, cette étude met en évidence un mécanisme par lequel les vésicules extracellulaires, porteuses de la protéine transmembranaire CSF-1 et sécrétées par les cellules cancéreuses, améliorent le pronostic en favorisant la différenciation des monocytes en macrophages pro-inflammatoires
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.
Proceedings of the National Academy of Sciences , article en libre accès, 2022