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

被引：134

作者：

Krockenberger, Mathias ^{[1
,2
]}

Dombrowski, Yvonne ^{[1
,2
]}

Weidler, Claudia ^{[1
,2
]}

Ossadnik, Monika ^{[1
,2
]}

Hoenig, Arnd ^{[1
,2
]}

Haeusler, Sebastian ^{[1
]}

Voigt, Heike ^{[3
]}

Becker, Juergen C. ^{[3
]}

Leng, Lin ^{[5
]}

Steinle, Alexander ^{[4
]}

Weller, Michael ^{[7
]}

Bucala, Richard ^{[5
,6
]}

Dietl, Johannes ^{[1
]}

Wischhusen, Joerg ^{[1
,2
]}

机构：

[1] Univ Wurzburg, Dept Obstet & Gynecol, D-97080 Wurzburg, Germany

[2] Univ Wurzburg, Interdisciplinary Ctr Clin Res, D-97080 Wurzburg, Germany

[3] Univ Wurzburg, Clin Res Grp KFO 124, D-97080 Wurzburg, Germany

[4] Univ Tubingen, Inst Cell Biol, Dept Immunol, Tubingen, Germany

[5] Yale Univ, Sch Med, Dept Med, New Haven, CT 06520 USA

[6] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA

[7] Univ Zurich Hosp, Dept Neurol, CH-8091 Zurich, Switzerland

来源：

JOURNAL OF IMMUNOLOGY | 2008年 / 180卷 / 11期

关键词：

D O I：

10.4049/jimmunol.180.11.7338

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：7338 / 7348

页数：11

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