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Suppression of Antitumor Immunity by Stromal Cells Expressing Fibroblast Activation Protein–α

2010; American Association for the Advancement of Science; Volume: 330; Issue: 6005 Linguagem: Inglês

10.1126/science.1195300

1095-9203

Matthew Kraman, Paul Bambrough, James N. Arnold, Edward W. Roberts, Łukasz Magiera, James O. Jones, Aarthi Gopinathan, David A. Tuveson, Douglas T. Fearon,

Ubiquitin and proteasome pathways

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.