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67. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Koreanischen Gesellschaft für Neurochirurgie (KNS)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

12. - 15. Juni 2016, Frankfurt am Main

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MIF-CD74 signaling impedes microglial M1 polarization and facilitates brain tumorigenesis

Meeting Abstract

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  • Ilker Eyüpoglu - Neurochirurgische Klinik, Universitätsklinikum Erlangen, Germany
  • Ali Ghoochani - Neurochirurgische Klinik, Universitätsklinikum Erlangen, Germany
  • Richard Bucala - Yale University School of Medicine, New Haven, Connecticut, USA
  • Nicolai E. Savaskan - Neurochirurgische Klinik, Universitätsklinikum Erlangen, Germany
  • Michael Buchfelder - Neurochirurgische Klinik, Universitätsklinikum Erlangen, Germany

Deutsche Gesellschaft für Neurochirurgie. 67. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 1. Joint Meeting mit der Koreanischen Gesellschaft für Neurochirurgie (KNS). Frankfurt am Main, 12.-15.06.2016. Düsseldorf: German Medical Science GMS Publishing House; 2016. DocMI.02.03

doi: 10.3205/16dgnc237, urn:nbn:de:0183-16dgnc2376

Veröffentlicht: 8. Juni 2016

© 2016 Eyüpoglu et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.

Gliederung

Text

Objective: Microglial cells in the brain tumor microenvironment are associated with enhanced glioma malignancy. They persist in an immunosuppressive M2 state at the peritumoral site and promote the growth of gliomas.

Method: In vitro, ex vivo, and in vivo techniques are used.

Results: Here, we investigated the underlying factors contributing to the abolished immune surveillance. We show that brain tumors escape pro-inflammatory M1 conversion of microglia via CD74 activation through the secretion of the cytokine MIF, which results in a M2 shift of microglial cells. Interruption of this glioma-microglial interaction through an antibody-neutralizing approach or siRNA-mediated inhibition prolongs survival time in glioma-implanted mice by reinstating the microglial pro-inflammatory M1 function. We show that MIF-CD74 signaling inhibits IFN-gamma secretion in microglia through phosphorylation of microglial ERK1/2. The inhibition of MIF signaling or its receptor CD74 promotes IFN-gamma release and amplifies tumor death either through pharmacological inhibition or through siRNA mediated knock down. The reinstated IFN-gamma secretion leads both to direct inhibition of glioma growth as well as inducing a M2 to M1 shift in glioma-associated microglia.

Conclusions: Our data reveal that interference with the MIF signaling pathway represents a viable therapeutic option for the restoration of IFN-gamma driven immune surveillance.