Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha

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)

URL: http://www.ncbi.nlm.nih.gov/pubmed/21051638
DOI: 10.1126/science.1195300

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: http://repository.cshl.edu/id/eprint/31648

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