Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein–α

M Kraman, PJ Bambrough, JN Arnold, EW Roberts… - Science, 2010 - science.org
M Kraman, PJ Bambrough, JN Arnold, EW Roberts, L Magiera, JO Jones, A Gopinathan…
Science, 2010science.org
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 …
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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