Suppression of Antitumor Immunity by Stromal Cells Expressing Fibroblast Activation Protein-{alpha}.

Science. 2010 Nov 5;330(6005):827-30.
Suppression of Antitumor Immunity by Stromal Cells Expressing Fibroblast Activation Protein-{alpha}.
Kraman M, Bambrough PJ, Arnold JN, Roberts EW, Magiera L, Jones JO, Gopinathan A, Tuveson DA, Fearon DT.

Wellcome Trust Immunology Unit, Department of Medicine, University of Cambridge, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, UK.
Abstract
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.