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J Immunol. 2008 Jun 1;180(11):7338-48.

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

Author information

1
Department for Obstetrics and Gynecology, University of Würzburg, Würzburg, Germany.

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.

PMID:
18490733
PMCID:
PMC3607742
DOI:
10.4049/jimmunol.180.11.7338
[Indexed for MEDLINE]
Free PMC Article

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