Macrophage migration inhibitory factor contributes to the immune escape of ovarian cancer by down-regulating NKG2D

Mathias Krockenberger; Yvonne Dombrowski; Claudia Weidler; Monika Ossadnik; Arnd Hönig; Sebastian Häusler; Heike Voigt; Jürgen C Becker; Lin Leng; Alexander Steinle; Michael Weller; Richard Bucala; Johannes Dietl; Jörg Wischhusen

Macrophage migration inhibitory factor contributes to the immune escape of ovarian cancer by down-regulating NKG2D

Mathias Krockenberger, Yvonne Dombrowski, Claudia Weidler, Monika Ossadnik, Arnd Hönig, Sebastian Häusler, Heike Voigt, Jürgen C Becker, Lin Leng, Alexander Steinle, Michael Weller, Richard Bucala, Johannes Dietl, Jörg Wischhusen

School of Medicine, Dentistry and Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

107 Citations (Scopus)

Abstract

The proinflammatory cytokine macrophage migration inhibitory factor (MIF) stimulates tumor cell proliferation, migration, and metastasis; promotes tumor angiogenesis; suppresses p53-mediated apoptosis; and inhibits antitumor immunity by largely unknown mechanisms. We here describe an overexpression of MIF in ovarian cancer that correlates with malignancy and the presence of ascites. Functionally, we find that MIF may contribute to the immune escape of ovarian carcinoma by transcriptionally down-regulating NKG2D in vitro and in vivo which impairs NK cell cytotoxicity toward tumor cells. Together with the additional tumorigenic properties of MIF, this finding provides a rationale for novel small-molecule inhibitors of MIF to be used for the treatment of MIF-secreting cancers.

Original language	English
Pages (from-to)	7338-48
Number of pages	11
Journal	Journal of Immunology
Volume	180
Issue number	11
Publication status	Published - 01 Jun 2008

Keywords

Adult
Aged
Aged, 80 and over
Ascites
Cytotoxicity, Immunologic
Down-Regulation
Female
Gene Expression Regulation, Neoplastic
Humans
Killer Cells, Natural
Macrophage Migration-Inhibitory Factors
Middle Aged
NK Cell Lectin-Like Receptor Subfamily K
Ovarian Neoplasms
Receptors, Immunologic
Receptors, Natural Killer Cell
Transcription, Genetic
Transforming Growth Factor beta
Tumor Cells, Cultured
Tumor Escape

UN SDGs

This output contributes to the following Sustainable Development Goal(s)

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Krockenberger, Mathias ; Dombrowski, Yvonne ; Weidler, Claudia ; Ossadnik, Monika ; Hönig, Arnd ; Häusler, Sebastian ; Voigt, Heike ; Becker, Jürgen C ; Leng, Lin ; Steinle, Alexander ; Weller, Michael ; Bucala, Richard ; Dietl, Johannes ; Wischhusen, Jörg. / Macrophage migration inhibitory factor contributes to the immune escape of ovarian cancer by down-regulating NKG2D. In: Journal of Immunology. 2008 ; Vol. 180, No. 11. pp. 7338-48.

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title = "Macrophage migration inhibitory factor contributes to the immune escape of ovarian cancer by down-regulating NKG2D",

abstract = "The proinflammatory cytokine macrophage migration inhibitory factor (MIF) stimulates tumor cell proliferation, migration, and metastasis; promotes tumor angiogenesis; suppresses p53-mediated apoptosis; and inhibits antitumor immunity by largely unknown mechanisms. We here describe an overexpression of MIF in ovarian cancer that correlates with malignancy and the presence of ascites. Functionally, we find that MIF may contribute to the immune escape of ovarian carcinoma by transcriptionally down-regulating NKG2D in vitro and in vivo which impairs NK cell cytotoxicity toward tumor cells. Together with the additional tumorigenic properties of MIF, this finding provides a rationale for novel small-molecule inhibitors of MIF to be used for the treatment of MIF-secreting cancers.",

keywords = "Adult, Aged, Aged, 80 and over, Ascites, Cytotoxicity, Immunologic, Down-Regulation, Female, Gene Expression Regulation, Neoplastic, Humans, Killer Cells, Natural, Macrophage Migration-Inhibitory Factors, Middle Aged, NK Cell Lectin-Like Receptor Subfamily K, Ovarian Neoplasms, Receptors, Immunologic, Receptors, Natural Killer Cell, Transcription, Genetic, Transforming Growth Factor beta, Tumor Cells, Cultured, Tumor Escape",

author = "Mathias Krockenberger and Yvonne Dombrowski and Claudia Weidler and Monika Ossadnik and Arnd H{\"o}nig and Sebastian H{\"a}usler and Heike Voigt and Becker, {J{\"u}rgen C} and Lin Leng and Alexander Steinle and Michael Weller and Richard Bucala and Johannes Dietl and J{\"o}rg Wischhusen",

year = "2008",

month = jun,

day = "1",

language = "English",

volume = "180",

pages = "7338--48",

journal = "Journal of Immunology",

issn = "0022-1767",

publisher = "American Association of Immunologists",

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Macrophage migration inhibitory factor contributes to the immune escape of ovarian cancer by down-regulating NKG2D. / Krockenberger, Mathias; Dombrowski, Yvonne; Weidler, Claudia; Ossadnik, Monika; Hönig, Arnd; Häusler, Sebastian; Voigt, Heike; Becker, Jürgen C; Leng, Lin; Steinle, Alexander; Weller, Michael; Bucala, Richard; Dietl, Johannes; Wischhusen, Jörg.

In: Journal of Immunology, Vol. 180, No. 11, 01.06.2008, p. 7338-48.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Macrophage migration inhibitory factor contributes to the immune escape of ovarian cancer by down-regulating NKG2D

AU - Krockenberger, Mathias

AU - Dombrowski, Yvonne

AU - Weidler, Claudia

AU - Ossadnik, Monika

AU - Hönig, Arnd

AU - Häusler, Sebastian

AU - Voigt, Heike

AU - Becker, Jürgen C

AU - Leng, Lin

AU - Steinle, Alexander

AU - Weller, Michael

AU - Bucala, Richard

AU - Dietl, Johannes

AU - Wischhusen, Jörg

PY - 2008/6/1

Y1 - 2008/6/1

N2 - The proinflammatory cytokine macrophage migration inhibitory factor (MIF) stimulates tumor cell proliferation, migration, and metastasis; promotes tumor angiogenesis; suppresses p53-mediated apoptosis; and inhibits antitumor immunity by largely unknown mechanisms. We here describe an overexpression of MIF in ovarian cancer that correlates with malignancy and the presence of ascites. Functionally, we find that MIF may contribute to the immune escape of ovarian carcinoma by transcriptionally down-regulating NKG2D in vitro and in vivo which impairs NK cell cytotoxicity toward tumor cells. Together with the additional tumorigenic properties of MIF, this finding provides a rationale for novel small-molecule inhibitors of MIF to be used for the treatment of MIF-secreting cancers.

AB - The proinflammatory cytokine macrophage migration inhibitory factor (MIF) stimulates tumor cell proliferation, migration, and metastasis; promotes tumor angiogenesis; suppresses p53-mediated apoptosis; and inhibits antitumor immunity by largely unknown mechanisms. We here describe an overexpression of MIF in ovarian cancer that correlates with malignancy and the presence of ascites. Functionally, we find that MIF may contribute to the immune escape of ovarian carcinoma by transcriptionally down-regulating NKG2D in vitro and in vivo which impairs NK cell cytotoxicity toward tumor cells. Together with the additional tumorigenic properties of MIF, this finding provides a rationale for novel small-molecule inhibitors of MIF to be used for the treatment of MIF-secreting cancers.

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KW - Aged

KW - Aged, 80 and over

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KW - Cytotoxicity, Immunologic

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KW - Female

KW - Gene Expression Regulation, Neoplastic

KW - Humans

KW - Killer Cells, Natural

KW - Macrophage Migration-Inhibitory Factors

KW - Middle Aged

KW - NK Cell Lectin-Like Receptor Subfamily K

KW - Ovarian Neoplasms

KW - Receptors, Immunologic

KW - Receptors, Natural Killer Cell

KW - Transcription, Genetic

KW - Transforming Growth Factor beta

KW - Tumor Cells, Cultured

KW - Tumor Escape

M3 - Article

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JO - Journal of Immunology

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