巨噬细胞移动抑制因子通过下调NKG2D促进卵巢癌的免疫逃逸。
Macrophage migration inhibitory factor contributes to the immune escape of ovarian cancer by down-regulating NKG2D.
作者信息
Krockenberger Mathias, Dombrowski Yvonne, Weidler Claudia, Ossadnik Monika, Hönig Arnd, Häusler Sebastian, Voigt Heike, Becker Jürgen C, Leng Lin, Steinle Alexander, Weller Michael, Bucala Richard, Dietl Johannes, Wischhusen Jörg
机构信息
Department for Obstetrics and Gynecology, University of Würzburg, Würzburg, Germany.
出版信息
J Immunol. 2008 Jun 1;180(11):7338-48. doi: 10.4049/jimmunol.180.11.7338.
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.
摘要
促炎细胞因子巨噬细胞移动抑制因子（MIF）可刺激肿瘤细胞增殖、迁移和转移；促进肿瘤血管生成；抑制p53介导的细胞凋亡；并通过 largely unknown mechanisms抑制抗肿瘤免疫。我们在此描述了MIF在卵巢癌中的过表达，其与恶性程度和腹水的存在相关。在功能上，我们发现MIF可能通过在体外和体内转录下调NKG2D来促进卵巢癌的免疫逃逸，这会损害NK细胞对肿瘤细胞的细胞毒性。连同MIF的其他致瘤特性，这一发现为新型MIF小分子抑制剂用于治疗分泌MIF的癌症提供了理论依据。
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