Senior Research Scientist at AstraZeneca
Research
Supervisor: Professor Douglas Fearon
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.
Publications
Arnold JN, Magiera L, Kraman M, Fearon DT. Tumoral Immune Suppression by Macrophages Expressing Fibroblast Activation Protein-α and Heme Oxygenase. Cancer Immunol Res. 2014 Feb;2(2):121-6.
Thaventhiran JE, Hoffmann A, Magiera L, de la Roche M, Lingel H, Brunner-Weinzierl M, Fearon DT. Activation of the Hippo pathway by CTLA-4 regulates the expression of Blimp-1 in the CD8+ T cell. Proc Natl Acad Sci U S A. 2012 Aug 14;109(33):E2223-9.
Kraman M, Bambrough PJ, Arnold JN, Roberts EW, Magiera L, Jones JO, Gopinathan A, Tuveson DA, Fearon DT. Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha. Science. 2010 Nov 5;330(6005):827-30.
Smagur J, Guzik K, Magiera L, Bzowska M, Gruca M, Thøgersen IB, Enghild JJ, Potempa J. A new pathway of staphylococcal pathogenesis: apoptosis-like death induced by Staphopain B in human neutrophils and monocytes.J Innate Immun. 2009;1(2):98-108.
