Details

Autor(en) / Beteiligte

• Givel, Anne-Marie
• Kieffer, Yann
• Scholer-Dahirel, Alix
• Sirven, Philemon
• Cardon, Melissa
• Pelon, Floriane
• Magagna, Ilaria
• Gentric, Géraldine
• Costa, Ana
• Bonneau, Claire
• Mieulet, Virginie
• Vincent-Salomon, Anne
• Mechta-Grigoriou, Fatima

Titel

miR200-regulated CXCL12β promotes fibroblast heterogeneity and immunosuppression in ovarian cancers

Ist Teil von

• Nature communications, 2018-03, Vol.9 (1), p.1056-20, Article 1056

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• High-grade serous ovarian cancers (HGSOC) have been subdivided into molecular subtypes. The mesenchymal HGSOC subgroup, defined by stromal-related gene signatures, is invariably associated with poor patient survival. We demonstrate that stroma exerts a key function in mesenchymal HGSOC. We highlight stromal heterogeneity in HGSOC by identifying four subsets of carcinoma-associated fibroblasts (CAF-S1-4). Mesenchymal HGSOC show high content in CAF-S1 fibroblasts, which exhibit immunosuppressive functions by increasing attraction, survival, and differentiation of CD25 FOXP3 T lymphocytes. The beta isoform of the CXCL12 chemokine (CXCL12β) specifically accumulates in the immunosuppressive CAF-S1 subset through a miR-141/200a dependent-mechanism. Moreover, CXCL12β expression in CAF-S1 cells plays a crucial role in CAF-S1 immunosuppressive activity and is a reliable prognosis factor in HGSOC, in contrast to CXCL12α. Thus, our data highlight the differential regulation of the CXCL12α and CXCL12β isoforms in HGSOC, and reveal a CXCL12β-associated stromal heterogeneity and immunosuppressive environment in mesenchymal HGSOC.