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

Research output: Contribution to journalArticle

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

Original languageEnglish
Pages (from-to)827-830
Number of pages4
JournalScience
Volume330
Issue number6005
DOIs
Publication statusPublished - Nov 2010

King's Authors

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.

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