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Tumoral immune suppression by macrophages expressing fibroblast activation protein-α and heme oxygenase-1.

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Tumoral immune suppression by macrophages expressing fibroblast activation protein-α and heme oxygenase-1. / Arnold, James Noble; Magiera, Lukasz; Kraman, Matthew; fearon, Douglas.

In: Cancer immunology research, 02.02.2014, p. 121-126.

Research output: Contribution to journalArticle

Harvard

Arnold, JN, Magiera, L, Kraman, M & fearon, D 2014, 'Tumoral immune suppression by macrophages expressing fibroblast activation protein-α and heme oxygenase-1.', Cancer immunology research, pp. 121-126.

APA

Arnold, J. N., Magiera, L., Kraman, M., & fearon, D. (2014). Tumoral immune suppression by macrophages expressing fibroblast activation protein-α and heme oxygenase-1. Cancer immunology research, 121-126.

Vancouver

Arnold JN, Magiera L, Kraman M, fearon D. Tumoral immune suppression by macrophages expressing fibroblast activation protein-α and heme oxygenase-1. Cancer immunology research. 2014 Feb 2;121-126.

Author

Arnold, James Noble ; Magiera, Lukasz ; Kraman, Matthew ; fearon, Douglas. / Tumoral immune suppression by macrophages expressing fibroblast activation protein-α and heme oxygenase-1. In: Cancer immunology research. 2014 ; pp. 121-126.

Bibtex Download

@article{7d0f34c67c4c42c3a6fa790ae051df07,
title = "Tumoral immune suppression by macrophages expressing fibroblast activation protein-α and heme oxygenase-1.",
abstract = "The depletion of tumor stromal cells that are marked by their expression of the membrane protein fibroblast activation protein-α (FAP) overcomes immune suppression and allows an anticancer cell immune response to control tumor growth. In subcutaneous tumors established with immunogenic Lewis lung carcinoma cells expressing ovalbumin (LL2/OVA), the FAP(+) population is comprised of CD45(+) and CD45(-) cells. In the present study, we further characterize the tumoral FAP(+)/CD45(+) population as a minor subpopulation of F4/80(hi)/CCR2(+)/CD206(+) M2 macrophages. Using bone marrow chimeric mice in which the primate diphtheria toxin receptor is restricted either to the FAP(+)/CD45(+) or to the FAP(+)/CD45(-) subset, we demonstrate by conditionally depleting each subset that both independently contribute to the immune-suppressive tumor microenvironment. A basis for the function of the FAP(+)/CD45(+) subset is shown to be the immune inhibitory enzyme, heme oxygenase-1 (HO-1). The FAP(+)/CD45(+) cells are the major tumoral source of HO-1, and an inhibitor of HO-1, Sn mesoporphyrin, causes the same extent of immune-dependent arrest of LL2/OVA tumor growth as does the depletion of these cells. Because this observation of immune suppression by HO-1 expressed by the FAP(+)/CD45(+) stromal cell is replicated in a transplanted model of pancreatic ductal adenocarcinoma, we conclude that pharmacologically targeting this enzyme may improve cancer immunotherapy.",
author = "Arnold, {James Noble} and Lukasz Magiera and Matthew Kraman and Douglas fearon",
year = "2014",
month = "2",
day = "2",
language = "English",
pages = "121--126",
journal = "Cancer immunology research",
issn = "2326-6074",
publisher = "American Association for Cancer Research Inc.",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Tumoral immune suppression by macrophages expressing fibroblast activation protein-α and heme oxygenase-1.

AU - Arnold, James Noble

AU - Magiera, Lukasz

AU - Kraman, Matthew

AU - fearon, Douglas

PY - 2014/2/2

Y1 - 2014/2/2

N2 - The depletion of tumor stromal cells that are marked by their expression of the membrane protein fibroblast activation protein-α (FAP) overcomes immune suppression and allows an anticancer cell immune response to control tumor growth. In subcutaneous tumors established with immunogenic Lewis lung carcinoma cells expressing ovalbumin (LL2/OVA), the FAP(+) population is comprised of CD45(+) and CD45(-) cells. In the present study, we further characterize the tumoral FAP(+)/CD45(+) population as a minor subpopulation of F4/80(hi)/CCR2(+)/CD206(+) M2 macrophages. Using bone marrow chimeric mice in which the primate diphtheria toxin receptor is restricted either to the FAP(+)/CD45(+) or to the FAP(+)/CD45(-) subset, we demonstrate by conditionally depleting each subset that both independently contribute to the immune-suppressive tumor microenvironment. A basis for the function of the FAP(+)/CD45(+) subset is shown to be the immune inhibitory enzyme, heme oxygenase-1 (HO-1). The FAP(+)/CD45(+) cells are the major tumoral source of HO-1, and an inhibitor of HO-1, Sn mesoporphyrin, causes the same extent of immune-dependent arrest of LL2/OVA tumor growth as does the depletion of these cells. Because this observation of immune suppression by HO-1 expressed by the FAP(+)/CD45(+) stromal cell is replicated in a transplanted model of pancreatic ductal adenocarcinoma, we conclude that pharmacologically targeting this enzyme may improve cancer immunotherapy.

AB - The depletion of tumor stromal cells that are marked by their expression of the membrane protein fibroblast activation protein-α (FAP) overcomes immune suppression and allows an anticancer cell immune response to control tumor growth. In subcutaneous tumors established with immunogenic Lewis lung carcinoma cells expressing ovalbumin (LL2/OVA), the FAP(+) population is comprised of CD45(+) and CD45(-) cells. In the present study, we further characterize the tumoral FAP(+)/CD45(+) population as a minor subpopulation of F4/80(hi)/CCR2(+)/CD206(+) M2 macrophages. Using bone marrow chimeric mice in which the primate diphtheria toxin receptor is restricted either to the FAP(+)/CD45(+) or to the FAP(+)/CD45(-) subset, we demonstrate by conditionally depleting each subset that both independently contribute to the immune-suppressive tumor microenvironment. A basis for the function of the FAP(+)/CD45(+) subset is shown to be the immune inhibitory enzyme, heme oxygenase-1 (HO-1). The FAP(+)/CD45(+) cells are the major tumoral source of HO-1, and an inhibitor of HO-1, Sn mesoporphyrin, causes the same extent of immune-dependent arrest of LL2/OVA tumor growth as does the depletion of these cells. Because this observation of immune suppression by HO-1 expressed by the FAP(+)/CD45(+) stromal cell is replicated in a transplanted model of pancreatic ductal adenocarcinoma, we conclude that pharmacologically targeting this enzyme may improve cancer immunotherapy.

M3 - Article

SP - 121

EP - 126

JO - Cancer immunology research

JF - Cancer immunology research

SN - 2326-6074

ER -

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