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

Research output: Contribution to journalArticlepeer-review

111 Citations (Scopus)


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 languageEnglish
Pages (from-to)7338-48
Number of pages11
JournalJournal of Immunology
Issue number11
Publication statusPublished - 01 Jun 2008


  • 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


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