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Depletion of Carcinoma-Associated Fibroblasts and Fibrosis Induces Immunosuppression and Accelerates Pancreas Cancer with Reduced Survival.
- Source :
-
Cancer Cell . Jun2014, Vol. 25 Issue 6, p719-734. 16p. - Publication Year :
- 2014
-
Abstract
- Summary: 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15356108
- Volume :
- 25
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Cancer Cell
- Publication Type :
- Academic Journal
- Accession number :
- 96660939
- Full Text :
- https://doi.org/10.1016/j.ccr.2014.04.005