Publikationsdatum:
2010-11-06
Beschreibung:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Kraman, Matthew -- Bambrough, Paul J -- Arnold, James N -- Roberts, Edward W -- Magiera, Lukasz -- Jones, James O -- Gopinathan, Aarthi -- Tuveson, David A -- Fearon, Douglas T -- Cancer Research UK/United Kingdom -- Wellcome Trust/United Kingdom -- New York, N.Y. -- Science. 2010 Nov 5;330(6005):827-30. doi: 10.1126/science.1195300.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Wellcome Trust Immunology Unit, Department of Medicine, University of Cambridge, Medical Research Council Centre, Hills Road, Cambridge CB2 2QH, UK.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21051638" target="_blank"〉PubMed〈/a〉
Schlagwort(e):
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
Print ISSN:
0036-8075
Digitale ISSN:
1095-9203
Thema:
Biologie
,
Chemie und Pharmazie
,
Informatik
,
Medizin
,
Allgemeine Naturwissenschaft
,
Physik
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