Journal
SCIENCE
Volume 330, Issue 6005, Pages 827-830Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1195300
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Funding
- Wellcome Trust
- National Institutes for Health Research Cambridge Biomedical Research Centre
- Cancer Research UK
- Hutchison Whampoa
- University of Cambridge
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The stromal microenvironment of tumors, which is a mixture of hematopoietic and mesenchymal cells, suppresses immune control of tumor growth. A stromal cell type that was first identified in human cancers expresses fibroblast activation protein-alpha (FAP). We created a transgenic mouse in which FAP-expressing cells can be ablated. Depletion of FAP-expressing cells, which made up only 2% of all tumor cells in established Lewis lung carcinomas, caused rapid hypoxic necrosis of both cancer and stromal cells in immunogenic tumors by a process involving interferon-gamma and tumor necrosis factor-alpha. Depleting FAP-expressing cells in a subcutaneous model of pancreatic ductal adenocarcinoma also permitted immunological control of growth. Therefore, FAP-expressing cells are a nonredundant, immune-suppressive component of the tumor microenvironment.
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