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

Vaccination with tumor-specific antigens is one of several attempted therapies seeking to harness the immune system, but -- unfortunately -- this strategy has been unsuccessful, possibly because of the immunosuppressive properties of the tumor microenvironment. Kraman et al. (p. 827; see the Perspec... Full description

Journal Title: Science (New York N.Y.), November 5, 2010, Vol.330(6005), pp.827-830
Main Author: Kraman, Matthew
Other Authors: Bambrough, Paul J , Arnold, James N , Roberts, Edward W , Magiera, Lukasz , Jones, James O , Gopinathan, Aarthi , Tuveson, David A , Fearon, Douglas T
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1095-9203 ; DOI: 10.1126/science.1195300
Link: http://search.proquest.com/docview/762685759/?pq-origsite=primo
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recordid: proquest762685759
title: Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha.
format: Article
creator:
  • Kraman, Matthew
  • Bambrough, Paul J
  • Arnold, James N
  • Roberts, Edward W
  • Magiera, Lukasz
  • Jones, James O
  • Gopinathan, Aarthi
  • Tuveson, David A
  • Fearon, Douglas T
subjects:
  • Animals–Immunology
  • Antigens, Neoplasm–Administration & Dosage
  • Cancer Vaccines–Immunology
  • Carcinoma, Lewis Lung–Immunology
  • Carcinoma, Pancreatic Ductal–Pathology
  • Cell Hypoxia–Therapy
  • Cell Line, Tumor–Immunology
  • Cell Survival–Pathology
  • Gelatinases–Metabolism
  • Immune Tolerance–Immunology
  • Interferon-Gamma–Metabolism
  • Membrane Proteins–Metabolism
  • Mice–Metabolism
  • Mice, Transgenic–Immunology
  • Necrosis–Metabolism
  • Neoplasm Transplantation–Immunology
  • Serine Endopeptidases–Immunology
  • Stromal Cells–Metabolism
  • Tumor Microenvironment–Metabolism
  • Tumor Necrosis Factor-Alpha–Metabolism
  • Antigens, Neoplasm
  • Cancer Vaccines
  • Membrane Proteins
  • Tumor Necrosis Factor-Alpha
  • Interferon-Gamma
  • Serine Endopeptidases
  • Fibroblast Activation Protein Alpha
  • Gelatinases
ispartof: Science (New York, N.Y.), November 5, 2010, Vol.330(6005), pp.827-830
description: Vaccination with tumor-specific antigens is one of several attempted therapies seeking to harness the immune system, but -- unfortunately -- this strategy has been unsuccessful, possibly because of the immunosuppressive properties of the tumor microenvironment. Kraman et al. (p. 827; see the Perspective by Schreiber and Rowley ) have identified immunosuppressive cells of mesenchymal origin in mice comprising 2% of the tumor stromal cell population. They were identified by expression of the fibroblast activation protein-α. Deletion of these cells in lung or pancreatic cancers in mice allowed successful therapeutic vaccination against the tumors, which was dependent on the adaptive immune system and the cytokines interferon-γ and tumor necrosis factor-α. These findings reveal that multiple cell types contribute to the immunosuppressive tumor microenvironment and will inform therapeutic cancer vaccine design. [PUBLICATION ] The stromal microenvironment of tumors, which is a mixture...
language: eng
source:
identifier: E-ISSN: 1095-9203 ; DOI: 10.1126/science.1195300
fulltext: no_fulltext
issn:
  • 10959203
  • 1095-9203
url: Link


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titleSuppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha.
creatorKraman, Matthew ; Bambrough, Paul J ; Arnold, James N ; Roberts, Edward W ; Magiera, Lukasz ; Jones, James O ; Gopinathan, Aarthi ; Tuveson, David A ; Fearon, Douglas T
contributorKraman, Matthew (correspondence author) ; Kraman, Matthew (record owner)
ispartofScience (New York, N.Y.), November 5, 2010, Vol.330(6005), pp.827-830
identifierE-ISSN: 1095-9203 ; DOI: 10.1126/science.1195300
subjectAnimals–Immunology ; Antigens, Neoplasm–Administration & Dosage ; Cancer Vaccines–Immunology ; Carcinoma, Lewis Lung–Immunology ; Carcinoma, Pancreatic Ductal–Pathology ; Cell Hypoxia–Therapy ; Cell Line, Tumor–Immunology ; Cell Survival–Pathology ; Gelatinases–Metabolism ; Immune Tolerance–Immunology ; Interferon-Gamma–Metabolism ; Membrane Proteins–Metabolism ; Mice–Metabolism ; Mice, Transgenic–Immunology ; Necrosis–Metabolism ; Neoplasm Transplantation–Immunology ; Serine Endopeptidases–Immunology ; Stromal Cells–Metabolism ; Tumor Microenvironment–Metabolism ; Tumor Necrosis Factor-Alpha–Metabolism ; Antigens, Neoplasm ; Cancer Vaccines ; Membrane Proteins ; Tumor Necrosis Factor-Alpha ; Interferon-Gamma ; Serine Endopeptidases ; Fibroblast Activation Protein Alpha ; Gelatinases
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descriptionVaccination with tumor-specific antigens is one of several attempted therapies seeking to harness the immune system, but -- unfortunately -- this strategy has been unsuccessful, possibly because of the immunosuppressive properties of the tumor microenvironment. Kraman et al. (p. 827; see the Perspective by Schreiber and Rowley ) have identified immunosuppressive cells of mesenchymal origin in mice comprising 2% of the tumor stromal cell population. They were identified by expression of the fibroblast activation protein-α. Deletion of these cells in lung or pancreatic cancers in mice allowed successful therapeutic vaccination against the tumors, which was dependent on the adaptive immune system and the cytokines interferon-γ and tumor necrosis factor-α. These findings reveal that multiple cell types contribute to the immunosuppressive tumor microenvironment and will inform therapeutic cancer vaccine design. [PUBLICATION ] The stromal microenvironment of tumors, which is a mixture...
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titleSuppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha.
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