Open AccessMIF Receptor CD 74 is Restricted to Microglia/Macrophages, Associated with a M 1‐Polarized Immune Milieu and Prolonged Patient Survival in Gliomas
Author(s) -
Zeiner Pia S.,
Preusse Corinna,
Blank AnnaEva,
Zachskorn Cornelia,
Baumgarten Peter,
Caspary Lixi,
Braczynski Anne K.,
Weissenberger Jakob,
Bratzke Hansjürgen,
Reiß Sandy,
Pennartz Sandra,
Winkelmann Ria,
Senft Christian,
Plate Karl H.,
Wischhusen Jörg,
Stenzel Werner,
Harter Patrick N.,
Mittelbronn Michel
Publication year - 2015
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/bpa.12194
Subject(s) - cd74 , microglia , macrophage migration inhibitory factor , glioma , immune system , cancer research , biology , receptor , u87 , immunohistochemistry , antibody , immunology , in vivo , cytokine , major histocompatibility complex , mhc class ii , inflammation , biochemistry , microbiology and biotechnology
The macrophage migration inhibitory factor ( MIF ) receptor CD 74 is overexpressed in various neoplasms, mainly in hematologic tumors, and currently investigated in clinical studies. CD 74 is quickly internalized and recycles after antibody binding, therefore it constitutes an attractive target for antibody‐based treatment strategies. CD 74 has been further described as one of the most up‐regulated molecules in human glioblastomas. To assess the potential relevance for anti‐ CD 74 treatment, we determined the cellular source and clinicopathologic relevance of CD 74 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 CD 74 expression in cellular fractions with whole tumor lysates. Our results show that CD 74 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 CD 74‐positive GAMs was associated with beneficial patient survival constituting an independent prognostic parameter and with an anti‐tumoral M 1 polarization. In summary, CD 74 expression in human gliomas is restricted to GAMs and positively associated with patient survival. In conclusion, CD 74 represents a positive prognostic marker most probably because of its association with an M 1‐polarized immune milieu in high‐grade gliomas.