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Kraman, Matthew; Bambrough, Paul J; Arnold, James N; Roberts, Edward W; Magiera, Lukasz; Jones, James O; Gopinathan, Aarthi; Tuveson, David A; Fearon, Douglas T
Science (American Association for the Advancement of Science), 11/2010, Volume: 330, Issue: 6005Journal Article
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-α (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-γ and tumor necrosis factor-α. 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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