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


Krockenberger, M; Dombrowski, Y; Weidler, C; Ossadnik, M; Hönig, A; Häusler, S; Voigt, H; Becker, J C; Leng, L; Steinle, A; Weller, M; Bucala, R; Dietl, J; Wischhusen, J (2008). Macrophage migration inhibitory factor contributes to the immune escape of ovarian cancer by down-regulating NKG2D. Journal of Immunology, 180(11):7338-7348.

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.

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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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2008
Deposited On:08 Dec 2008 13:24
Last Modified:05 Apr 2016 12:39
Publisher:American Association of Immunologists
ISSN:0022-1767
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:10.4049/jimmunol.180.11.7338
Official URL:http://www.jimmunol.org/cgi/gca?sendit=Get+All+Checked+Abstract(s)&gca=180%2F11%2F7338
PubMed ID:18490733

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