| Autor: |
Monika Licaj, Rana Mhaidly, Yann Kieffer, Hugo Croizer, Claire Bonneau, Arnaud Meng, Lounes Djerroudi, Kevin Mujangi-Ebeka, Hocine R. Hocine, Brigitte Bourachot, Ilaria Magagna, Renaud Leclere, Lea Guyonnet, Mylene Bohec, Coralie Guérin, Sylvain Baulande, Maud Kamal, Christophe Le Tourneau, Fabrice Lecuru, Véronique Becette, Roman Rouzier, Anne Vincent-Salomon, Geraldine Gentric, Fatima Mechta-Grigoriou |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
|
| Zdroj: |
Nature Communications, Vol 15, Iss 1, Pp 1-27 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-024-45595-3 |
| Popis: |
Abstract Although cancer-associated fibroblast (CAF) heterogeneity is well-established, the impact of chemotherapy on CAF populations remains poorly understood. Here we address this question in high-grade serous ovarian cancer (HGSOC), in which we previously identified 4 CAF populations. While the global content in stroma increases in HGSOC after chemotherapy, the proportion of FAP+ CAF (also called CAF-S1) decreases. Still, maintenance of high residual CAF-S1 content after chemotherapy is associated with reduced CD8+ T lymphocyte density and poor patient prognosis, emphasizing the importance of CAF-S1 reduction upon treatment. Single cell analysis, spatial transcriptomics and immunohistochemistry reveal that the content in the ECM-producing ANTXR1+ CAF-S1 cluster (ECM-myCAF) is the most affected by chemotherapy. Moreover, functional assays demonstrate that ECM-myCAF isolated from HGSOC reduce CD8+ T-cell cytotoxicity through a Yes Associated Protein 1 (YAP1)-dependent mechanism. Thus, efficient inhibition after treatment of YAP1-signaling pathway in the ECM-myCAF cluster could enhance CD8+ T-cell cytotoxicity. Altogether, these data pave the way for therapy targeting YAP1 in ECM-myCAF in HGSOC. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
Full text from SpringerLink