| Literature DB >> 24856586 |
Berna C Özdemir1, Tsvetelina Pentcheva-Hoang2, Julienne L Carstens3, Xiaofeng Zheng3, Chia-Chin Wu4, Tyler R Simpson2, Hanane Laklai5, Hikaru Sugimoto1, Christoph Kahlert1, Sergey V Novitskiy6, Ana De Jesus-Acosta7, Padmanee Sharma2, Pedram Heidari8, Umar Mahmood8, Lynda Chin4, Harold L Moses6, Valerie M Weaver5, Anirban Maitra9, James P Allison2, Valerie S LeBleu1, Raghu Kalluri10.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is associated with marked fibrosis and stromal myofibroblasts, but their functional contribution remains unknown. Transgenic mice with the ability to delete αSMA(+) myofibroblasts in pancreatic cancer were generated. Depletion starting at either noninvasive precursor (pancreatic intraepithelial neoplasia) or the PDAC stage led to invasive, undifferentiated tumors with enhanced hypoxia, epithelial-to-mesenchymal transition, and cancer stem cells, with diminished animal survival. In PDAC patients, fewer myofibroblasts in their tumors also correlated with reduced survival. Suppressed immune surveillance with increased CD4(+)Foxp3(+) Tregs was observed in myofibroblast-depleted mouse tumors. Although myofibroblast-depleted tumors did not respond to gemcitabine, anti-CTLA4 immunotherapy reversed disease acceleration and prolonged animal survival. This study underscores the need for caution in targeting carcinoma-associated fibroblasts in PDAC.Entities:
Mesh：
Year: 2014 PMID： 24856586 PMCID： PMC4180632 DOI： 10.1016/j.ccr.2014.04.005
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743