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.
authors.affiliation: Department for Obstetrics and Gynecology, University of Würzburg, Würzburg, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Krockenberger
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Dombrowski
authors.forename: Claudia
authors.initials: C
authors.lastname: Weidler
authors.forename: Monika
authors.initials: M
authors.lastname: Ossadnik
authors.forename: Arnd
authors.initials: A
authors.lastname: Hönig
authors.forename: Sebastian
authors.initials: S
authors.lastname: Häusler
authors.forename: Heike
authors.initials: H
authors.lastname: Voigt
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Becker
authors.forename: Lin
authors.initials: L
authors.lastname: Leng
authors.forename: Alexander
authors.initials: A
authors.lastname: Steinle
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
authors.forename: Richard
authors.initials: R
authors.lastname: Bucala
authors.forename: Johannes
authors.initials: J
authors.lastname: Dietl
authors.forename: Jörg
authors.initials: J
authors.lastname: Wischhusen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001201:Ascites; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000276:immunology / Q000378:metabolism*; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D055607:Receptors, Natural Killer Cell; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D019139:Tumor Escape
chemical_list: C527085:KLRK1 protein, human; D008263:Macrophage Migration-Inhibitory Factors; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D016212:Transforming Growth Factor beta