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。
相似文献
1
Macrophage migration inhibitory factor contributes to the immune escape of ovarian cancer by down-regulating NKG2D.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。
J Immunol. 2008 Jun 1;180(11):7338-48. doi: 10.4049/jimmunol.180.11.7338.
2
Macrophage migration inhibitory factor (MIF) expression in human malignant gliomas contributes to immune escape and tumour progression.巨噬细胞移动抑制因子（MIF）在人恶性胶质瘤中的表达有助于免疫逃逸和肿瘤进展。
Acta Neuropathol. 2011 Sep;122(3):353-65. doi: 10.1007/s00401-011-0858-3. Epub 2011 Jul 21.
3
IL-2/IL-18 prevent the down-modulation of NKG2D by TGF-beta in NK cells via the c-Jun N-terminal kinase (JNK) pathway.白细胞介素-2/白细胞介素-18通过c-Jun氨基末端激酶（JNK）途径防止转化生长因子-β下调自然杀伤细胞中NKG2D的表达。
Cell Immunol. 2006 Jul;242(1):39-45. doi: 10.1016/j.cellimm.2006.09.002. Epub 2006 Oct 27.
4
RNA interference targeting transforming growth factor-beta enhances NKG2D-mediated antiglioma immune response, inhibits glioma cell migration and invasiveness, and abrogates tumorigenicity in vivo.靶向转化生长因子-β的RNA干扰增强NKG2D介导的抗胶质瘤免疫反应，抑制胶质瘤细胞迁移和侵袭，并消除体内致瘤性。
Cancer Res. 2004 Oct 15;64(20):7596-603. doi: 10.1158/0008-5472.CAN-04-1627.
5
Evasion from NK cell immunity by MHC class I chain-related molecules expressing colon adenocarcinoma.表达于结肠腺癌的MHC I类链相关分子对自然杀伤细胞免疫的逃逸
J Immunol. 2003 Dec 15;171(12):6891-9. doi: 10.4049/jimmunol.171.12.6891.
6
Elevated TGF-beta1 secretion and down-modulation of NKG2D underlies impaired NK cytotoxicity in cancer patients.转化生长因子β1分泌升高和自然杀伤细胞2D（NKG2D）下调是癌症患者自然杀伤细胞（NK）细胞毒性受损的基础。
J Immunol. 2004 Jun 15;172(12):7335-40. doi: 10.4049/jimmunol.172.12.7335.
7
Soluble ULBP suppresses natural killer cell activity via down-regulating NKG2D expression.可溶性ULBP通过下调NKG2D表达来抑制自然杀伤细胞活性。
Cell Immunol. 2006 Jan;239(1):22-30. doi: 10.1016/j.cellimm.2006.03.002. Epub 2006 Apr 21.
8
Inhibition of NK cell activity through TGF-beta 1 by down-regulation of NKG2D in a murine model of head and neck cancer.在头颈癌小鼠模型中，通过下调NKG2D，转化生长因子-β1抑制自然杀伤细胞活性。
J Immunol. 2005 Oct 15;175(8):5541-50. doi: 10.4049/jimmunol.175.8.5541.
9
Human uveal melanoma cells produce macrophage migration-inhibitory factor to prevent lysis by NK cells.人类葡萄膜黑色素瘤细胞产生巨噬细胞迁移抑制因子以防止被自然杀伤细胞裂解。
J Immunol. 2000 Jul 15;165(2):710-5. doi: 10.4049/jimmunol.165.2.710.
10
Maintenance of hair follicle immune privilege is linked to prevention of NK cell attack.毛囊免疫豁免的维持与防止自然杀伤细胞攻击有关。
J Invest Dermatol. 2008 May;128(5):1196-206. doi: 10.1038/sj.jid.5701183. Epub 2007 Dec 27.
引用本文的文献
1
Supercharged Natural Killer (sNK) Cells Inhibit Melanoma Tumor Progression and Restore Endogenous NK Cell Function in Humanized BLT Mice.增强型自然杀伤（sNK）细胞抑制黑色素瘤肿瘤进展并恢复人源化BLT小鼠的内源性NK细胞功能。
Cancers (Basel). 2025 Jul 23;17(15):2430. doi: 10.3390/cancers17152430.
2
Macrophage Migration Inhibitory Factor Suppresses Natural Killer Cell Response and Promotes Hypoimmunogenic Stem Cell Engraftment Following Spinal Cord Injury.巨噬细胞移动抑制因子抑制自然杀伤细胞反应并促进脊髓损伤后低免疫原性干细胞植入。
Biology (Basel). 2025 Jun 30;14(7):791. doi: 10.3390/biology14070791.
3
A Human Tumor-Immune Organoid Model of Glioblastoma.一种胶质母细胞瘤的人类肿瘤-免疫类器官模型。
bioRxiv. 2025 Jun 20:2025.06.16.660009. doi: 10.1101/2025.06.16.660009.
4
Macrophage Migration Inhibitory Factor Suppresses Natural Killer Cell Response and Promotes Hypoimmunogenic Stem Cell Engraftment Following Spinal Cord Injury.巨噬细胞迁移抑制因子抑制自然杀伤细胞反应并促进脊髓损伤后低免疫原性干细胞植入。
bioRxiv. 2025 May 7:2025.05.06.652516. doi: 10.1101/2025.05.06.652516.
5
Role of tumor microenvironment in ovarian cancer metastasis and clinical advancements.肿瘤微环境在卵巢癌转移及临床进展中的作用
J Transl Med. 2025 May 14;23(1):539. doi: 10.1186/s12967-025-06508-0.
6
Nanotechnology-based drug delivery system for the diagnosis and treatment of ovarian cancer.用于卵巢癌诊断与治疗的基于纳米技术的药物递送系统。
Discov Oncol. 2025 Mar 29;16(1):422. doi: 10.1007/s12672-025-02062-9.
7
Arachidonic acid impairs natural killer cell functions by disrupting signaling pathways driven by activating receptors and reactive oxygen species.花生四烯酸通过破坏激活受体和活性氧物种驱动的信号通路来损害自然杀伤细胞功能。
Cell Commun Signal. 2024 Nov 19;22(1):555. doi: 10.1186/s12964-024-01940-z.
8
Human NK cells and cancer.人自然杀伤细胞与癌症。
Oncoimmunology. 2024 Jul 16;13(1):2378520. doi: 10.1080/2162402X.2024.2378520. eCollection 2024.
9
New immune phenotypes for treatment response in high-grade serous ovarian carcinoma patients.高级别浆液性卵巢癌患者治疗反应的新型免疫表型。
Front Immunol. 2024 Jun 14;15:1394497. doi: 10.3389/fimmu.2024.1394497. eCollection 2024.
10
Natural killer cells in cancer immunotherapy.癌症免疫疗法中的自然杀伤细胞。
MedComm (2020). 2024 Jun 15;5(7):e626. doi: 10.1002/mco2.626. eCollection 2024 Jul.
本文引用的文献
1
Immunotherapy with chimeric NKG2D receptors leads to long-term tumor-free survival and development of host antitumor immunity in murine ovarian cancer.嵌合NKG2D受体免疫疗法可使小鼠卵巢癌实现长期无瘤生存并激发宿主抗肿瘤免疫。
J Immunol. 2008 Jan 1;180(1):72-8. doi: 10.4049/jimmunol.180.1.72.
2
MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment.巨噬细胞移动抑制因子（MIF）是炎症和致动脉粥样硬化细胞募集过程中CXC趋化因子受体的异源配体。
Nat Med. 2007 May;13(5):587-96. doi: 10.1038/nm1567. Epub 2007 Apr 15.
3
Macrophage migration inhibitory factor expression in ovarian cancer.巨噬细胞移动抑制因子在卵巢癌中的表达
Am J Obstet Gynecol. 2007 Apr;196(4):348.e1-5. doi: 10.1016/j.ajog.2006.12.030.
4
CD44 is the signaling component of the macrophage migration inhibitory factor-CD74 receptor complex.CD44是巨噬细胞移动抑制因子-CD74受体复合物的信号传导成分。
Immunity. 2006 Oct;25(4):595-606. doi: 10.1016/j.immuni.2006.08.020.
5
Targeting of CD44 eradicates human acute myeloid leukemic stem cells.靶向CD44可根除人类急性髓系白血病干细胞。
Nat Med. 2006 Oct;12(10):1167-74. doi: 10.1038/nm1483. Epub 2006 Sep 24.
6
TGF-beta and metalloproteinases differentially suppress NKG2D ligand surface expression on malignant glioma cells.转化生长因子-β和金属蛋白酶对恶性胶质瘤细胞表面NKG2D配体的表达有不同程度的抑制作用。
Brain. 2006 Sep;129(Pt 9):2416-25. doi: 10.1093/brain/awl205. Epub 2006 Aug 3.
7
MIF: a new cytokine link between rheumatoid arthritis and atherosclerosis.巨噬细胞移动抑制因子：类风湿关节炎与动脉粥样硬化之间新的细胞因子联系
Nat Rev Drug Discov. 2006 May;5(5):399-410. doi: 10.1038/nrd2029.
8
TLR-4 signaling promotes tumor growth and paclitaxel chemoresistance in ovarian cancer.Toll样受体4（TLR-4）信号传导促进卵巢癌的肿瘤生长和对紫杉醇的化疗耐药性。
Cancer Res. 2006 Apr 1;66(7):3859-68. doi: 10.1158/0008-5472.CAN-05-3948.
9
Tumor-derived macrophage migration inhibitory factor (MIF) inhibits T lymphocyte activation.肿瘤衍生的巨噬细胞移动抑制因子（MIF）抑制T淋巴细胞活化。
Cytokine. 2006 Feb 21;33(4):188-98. doi: 10.1016/j.cyto.2006.01.006. Epub 2006 Mar 7.
10
Inhibition of tumor growth and metastasis in vitro and in vivo by targeting macrophage migration inhibitory factor in human neuroblastoma.通过靶向人神经母细胞瘤中的巨噬细胞迁移抑制因子在体外和体内抑制肿瘤生长和转移
Oncogene. 2006 Jun 15;25(25):3501-8. doi: 10.1038/sj.onc.1209395. Epub 2006 Jan 30.
Zotero 插件