Kraman, M., Bambrough, P. J., Arnold, J. N., Roberts, E. W., Magiera, L., Jones, J. O., Gopinathan, A., Tuveson, D. A., Fearon, D. T. (November 2010) Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha. Science, 330 (6005). pp. 827-30. ISSN 1095-9203 (Electronic)0036-8075 (Linking)
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.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Animals Antigens, Neoplasm/immunology Cancer Vaccines/administration & dosage/immunology Carcinoma, Lewis Lung/ immunology/pathology/therapy Carcinoma, Pancreatic Ductal/ immunology/pathology Cell Hypoxia Cell Line, Tumor Cell Survival Gelatinases/ metabolism Immune Tolerance Interferon-gamma/immunology/metabolism Membrane Proteins/ metabolism Mice Mice, Transgenic Necrosis Neoplasm Transplantation Serine Endopeptidases/ metabolism Stromal Cells/ immunology/metabolism Tumor Microenvironment/ immunology Tumor Necrosis Factor-alpha/immunology/metabolism |
| Subjects: | organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts organs, tissues, organelles, cell types and functions > cell types and functions > cell types > fibroblasts bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > tumor suppressor |
| CSHL Authors: | |
| Communities: | CSHL labs > Fearon lab CSHL labs > Tuveson lab |
| Depositing User: | Matt Covey |
| Date: | 5 November 2010 |
| Date Deposited: | 22 Jul 2015 20:08 |
| Last Modified: | 22 Jul 2015 20:08 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/31648 |
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