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Science 330 (6005): 827-830

Copyright © 2010 by the American Association for the Advancement of Science

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

Matthew Kraman,1,* Paul J. Bambrough,1,* James N. Arnold,1,* Edward W. Roberts,1 Lukasz Magiera,1 James O. Jones,1 Aarthi Gopinathan,2,3 David A. Tuveson,2 Douglas T. Fearon1,{dagger}

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–{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.

1 Wellcome Trust Immunology Unit, Department of Medicine, University of Cambridge, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, UK.
2 Cancer Research UK Cambridge Research Institute, The Li Ka Shing Centre, Robinson Way, Cambridge CB2 ORE, UK.
3 Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: dtf1000{at}cam.ac.uk


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