Glioblastoma Myeloid-Derived Suppressor Cell Subsets Express Differential Macrophage Migration Inhibitory Factor Receptor Profiles That Can Be Targeted to Reduce Immune Suppression.
Animals
Brain Neoplasms
/ immunology
Glioblastoma
/ immunology
Humans
Immunotherapy
/ methods
Macrophage Migration-Inhibitory Factors
/ immunology
Mice
Myeloid-Derived Suppressor Cells
/ immunology
Pyridines
/ pharmacology
Receptors, Immunologic
/ immunology
Tumor Escape
/ drug effects
Tumor Microenvironment
/ drug effects
MDSC
MIF–macrophage migration inhibitory factor
glioma
immunesuppresion
immunetherapy
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
23
12
2019
accepted:
13
05
2020
entrez:
7
7
2020
pubmed:
7
7
2020
medline:
7
4
2021
Statut:
epublish
Résumé
The application of tumor immunotherapy to glioblastoma (GBM) is limited by an unprecedented degree of immune suppression due to factors that include high numbers of immune suppressive myeloid cells, the blood brain barrier, and T cell sequestration to the bone marrow. We previously identified an increase in immune suppressive myeloid-derived suppressor cells (MDSCs) in GBM patients, which correlated with poor prognosis and was dependent on macrophage migration inhibitory factor (MIF). Here we examine the MIF signaling axis in detail in murine MDSC models, GBM-educated MDSCs and human GBM. We found that the monocytic subset of MDSCs (M-MDSCs) expressed high levels of the MIF cognate receptor CD74 and was localized in the tumor microenvironment. In contrast, granulocytic MDSCs (G-MDSCs) expressed high levels of the MIF non-cognate receptor CXCR2 and showed minimal accumulation in the tumor microenvironment. Furthermore, targeting M-MDSCs with Ibudilast, a brain penetrant MIF-CD74 interaction inhibitor, reduced MDSC function and enhanced CD8 T cell activity in the tumor microenvironment. These findings demonstrate the MDSC subsets differentially express MIF receptors and may be leveraged for specific MDSC targeting.
Identifiants
pubmed: 32625208
doi: 10.3389/fimmu.2020.01191
pmc: PMC7315581
doi:
Substances chimiques
Macrophage Migration-Inhibitory Factors
0
Pyridines
0
Receptors, Immunologic
0
macrophage migration inhibitory factor receptor
0
ibudilast
M0TTH61XC5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1191Subventions
Organisme : NCI NIH HHS
ID : F32 CA243314
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007250
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS109742
Pays : United States
Organisme : NINDS NIH HHS
ID : F31 NS101771
Pays : United States
Informations de copyright
Copyright © 2020 Alban, Bayik, Otvos, Rabljenovic, Leng, Jia-Shiun, Roversi, Lauko, Momin, Mohammadi, Peereboom, Ahluwalia, Matsuda, Yun, Bucala, Vogelbaum and Lathia.
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