In:
Brain Pathology, Wiley, Vol. 25, No. 4 ( 2015-07), p. 491-504
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1015-6305
,
1750-3639
DOI:
10.1111/bpa.2015.25.issue-4
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2029927-8
Bookmarklink