Macrophage Migration Inhibitory Factor Contributes to the Immune Escape of Ovarian Cancer by Down-Regulating NKG2D
Mathias Krockenbergera b c d✉, Yvonne Dombrowskia b c d✉, Claudia Weidlera b c d✉, Monika Ossadnika b c d✉, Arnd Höniga b c d, Sebastian F. Häuslera c, Heike Voigte f, Jürgen Christian Beckere f, Lin Lengg h, Alexander Steinlei j, Michael Wellerk l, Richard Bucalag m n o, J. Dietla c✉, Jörg Wischhusena b c d
- aDepartment for Obstetrics and Gynecology, University of Würzburg , Würzburg
- bInterdisciplinary Center for Clinical Research, University of Würzburg , Würzburg
- c*Department for Obstetrics and Gynecology
- d†Interdisciplinary Center for Clinical Research, and
- eClinical research group KFO 124, University of Würzburg , Würzburg
- f‡Clinical research group KFO 124, University of Würzburg, Würzburg, Germany
- gDepartment of Medicine, Yale University School of Medicine , New Haven, CT 06520
- h¶Department of Medicine and
- iInstitute for Cell Biology, Department of Immunology, University of Tübingen , Tübingen
- j§Institute for Cell Biology, Department of Immunology, University of Tübingen, Tübingen, Germany
- kDepartment of Neurology, University Hospital Zurich , Zurich
- l#Department of Neurology, University Hospital Zurich, Zurich, Switzerland
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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.
TL;DRIt is found 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. (Semantic Scholar)

