MIF Receptor CD74 is Restricted to Microglia/Macrophages, Associated with a M1-Polarized Immune Milieu and Prolonged Patient Survival in Gliomas

被引：87

作者：

Zeiner, Pia S. ^{[1
]}

Preusse, Corinna ^{[6
]}

Blank, Anna-Eva ^{[1
]}

Zachskorn, Cornelia ^{[1
,7
,8
]}

Baumgarten, Peter ^{[1
,5
]}

Caspary, Lixi ^{[1
]}

Braczynski, Anne K. ^{[1
]}

Weissenberger, Jakob ^{[2
]}

Bratzke, Hansjuergen ^{[3
]}

Reiss, Sandy ^{[9
]}

Pennartz, Sandra ^{[9
]}

Winkelmann, Ria ^{[4
]}

Senft, Christian ^{[2
,5
,7
]}

Plate, Karl H. ^{[1
,7
,8
]}

Wischhusen, Joerg ^{[10
]}

Stenzel, Werner ^{[6
]}

Harter, Patrick N. ^{[1
,7
,8
]}

Mittelbronn, Michel ^{[1
,7
,8
]}

机构：

[1] Goethe Univ Frankfurt, Inst Neurol, Edinger Inst, D-60528 Frankfurt, Germany

[2] Goethe Univ Frankfurt, Dept Expt Neurosurg, D-60528 Frankfurt, Germany

[3] Goethe Univ Frankfurt, Inst Forens Med, D-60528 Frankfurt, Germany

[4] Goethe Univ Frankfurt, Senckenberg Inst Pathol, D-60528 Frankfurt, Germany

[5] Goethe Univ Frankfurt, Dept Neurosurg, D-60528 Frankfurt, Germany

[6] Charite, Dept Neuropathol, Berlin, Germany

[7] German Canc Consortium DKTK, Heidelberg, Germany

[8] German Canc Res Ctr, Heidelberg, Germany

[9] Miltenyi Biotec, Bergisch Gladbach, Germany

[10] Univ Wurzburg, Jr Res Grp Tumour Progress & Immune Escape, Dept Obstet & Gynecol, Interdisciplinary Ctr Clin Res, D-97070 Wurzburg, Germany

来源：

BRAIN PATHOLOGY | 2015年 / 25卷 / 04期

关键词：

CD74; glioma; immune polarization; MIF; MIGRATION-INHIBITORY FACTOR; CELL-SURVIVAL; UP-REGULATION; EXPRESSION; CANCER; ACTIVATION; ANGIOGENESIS; PATHWAY; BINDING; PROTEIN;

D O I：

10.1111/bpa.12194

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

The macrophage migration inhibitory factor (MIF) receptor CD74 is overexpressed in various neoplasms, mainly in hematologic tumors, and currently investigated in clinical studies. CD74 is quickly internalized and recycles after antibody binding, therefore it constitutes an attractive target for antibody-based treatment strategies. CD74 has been further described as one of the most up-regulated molecules in human glioblastomas. To assess the potential relevance for anti-CD74 treatment, we determined the cellular source and clinicopathologic relevance of CD74 expression in human gliomas by immunohistochemistry, immunofluorescence, immunoblotting, cell sorting analysis and quantitative polymerase chain reaction (qPCR). Furthermore, we fractionated glioblastoma cells and glioma-associated microglia/macrophages (GAMs) from primary tumors and compared CD74 expression in cellular fractions with whole tumor lysates. Our results show that CD74 is restricted to GAMsin vivo, while being absent in tumor cells, the latter strongly expressing its ligand MIF. Most interestingly, a higher amount of CD74-positive GAMs was associated with beneficial patient survival constituting an independent prognostic parameter and with an anti-tumoral M1 polarization. In summary, CD74 expression in human gliomas is restricted to GAMs and positively associated with patient survival. In conclusion, CD74 represents a positive prognostic marker most probably because of its association with an M1-polarized immune milieu in high-grade gliomas.

引用

页码：491 / 504

页数：14

共 33 条

[1] ISO-1 binding to the tautomerase active site of MIF inhibits its pro-inflammatory activity and increases survival in severe sepsis [J].