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

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          Abstract

          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 GAMs in 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.

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          Author and article information

          Journal
          Brain Pathol.
          Brain pathology (Zurich, Switzerland)
          Wiley-Blackwell
          1750-3639
          1015-6305
          Jul 2015
          : 25
          : 4
          Affiliations
          [1 ] Edinger Institute, Institute of Neurology, Goethe University Frankfurt, Frankfurt am Main, Germany.
          [2 ] Department of Neuropathology, Charité, Berlin, Germany.
          [3 ] German Cancer Consortium (DKTK), Heidelberg, Germany.
          [4 ] German Cancer Research Center (DKFZ), Heidelberg, Germany.
          [5 ] Department of Neurosurgery, Goethe University Frankfurt, Frankfurt am Main, Germany.
          [6 ] Department of Experimental Neurosurgery, Goethe University Frankfurt, Frankfurt am Main, Germany.
          [7 ] Institute of Forensic Medicine, Goethe University Frankfurt, Frankfurt am Main, Germany.
          [8 ] Miltenyi Biotec, Bergisch Gladbach, Germany.
          [9 ] Senckenberg Institute of Pathology, Goethe University Frankfurt, Frankfurt am Main, Germany.
          [10 ] Junior Research Group "Tumour Progression and Immune Escape", Interdisciplinary Center for Clinical Research, Department for Obstetrics and Gynecology, University of Würzburg, Würzburg, Germany.
          Article
          10.1111/bpa.12194
          25175718
          a0d12b19-d8fe-4d08-a875-7da1ad5a97bf
          History

          CD74,MIF,glioma,immune polarization
          CD74, MIF, glioma, immune polarization

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