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Review
. 2024 Aug 10;6(1):vdae142.
doi: 10.1093/noajnl/vdae142. eCollection 2024 Jan-Dec.

Macrophage migration inhibitory factor as a therapeutic target in neuro-oncology: A review

Jakub Jarmula  1 , Juyeun Lee  2 , Adam Lauko  1 , Prajwal Rajappa  3 , Matthew M Grabowski  1   2   4   5 , Andrew Dhawan  1   2   5 , Peiwen Chen  1   6 , Richard Bucala  7 , Michael A Vogelbaum  8 , Justin D Lathia  1   2   4   5
Affiliations
Review

Macrophage migration inhibitory factor as a therapeutic target in neuro-oncology: A review

Jakub Jarmula et al. Neurooncol Adv. .

Abstract

Primary central nervous system (CNS) tumors affect tens of thousands of patients each year, and there is a significant need for new treatments. Macrophage migration inhibitory factor (MIF) is a cytokine implicated in multiple tumorigenic processes such as cell proliferation, vascularization, and immune evasion and is therefore a promising therapeutic target in primary CNS tumors. There are several MIF-directed treatments available, including small-molecule inhibitors, peptide drugs, and monoclonal antibodies. However, only a small number of these drugs have been tested in preclinical models of primary CNS tumors, and even fewer have been studied in patients. Moreover, the brain has unique therapeutic requirements that further make effective targeting challenging. In this review, we summarize the latest functions of MIF in primary CNS tumor initiation and progression. We also discuss advances in MIF therapeutic development and ongoing preclinical studies and clinical trials. Finally, we discuss potential future MIF therapies and the strategies required for successful clinical translation.

Keywords: glioblastoma; macrophage migration inhibitory factor; tumor microenvironment.

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Conflict of interest statement

R.B. serves on the clinical advisory board for OncoOne and is an inventor on Yale managed patents for therapeutic MIF antagonists. M.A.V. reports institutional clinical trial contracts with Infuseon, Oncosynergy, and DeNovo; Honoraria from Biodexa, Servier; and being named as a coinventor on pending and issued patents held by the Cleveland Clinic and Moffitt Cancer Center relating to cancer therapies, but these are not directly relevant to this review. J.D.L. reports being named as a coinventor on pending and issued patents held by the Cleveland Clinic relating to cancer therapies, but these are not directly relevant to this review.

Figures

Figure 1.
Figure 1.
MIF-mediated signaling pathways in primary CNS tumors. CXCR2 = chemokine C-X-C motif receptor 2; G-MDSC = granulocytic myeloid-derived suppressor cell; GBM = glioblastoma; IFN-g = interferon gamma; M-MDSC = monocytic myeloid-derived suppressor cell; MIF = macrophage migration inhibitory factor; MCP-1 = monocyte chemoattractant protein-1; NK = natural killer cell; NKG2D = natural killer group 2 member D receptor.
Figure 2.
Figure 2.
The effects of MIF on GBM behavior. CXCR2 = chemokine C-X-C motif receptor 2; CXCR4 = chemokine C-X-C motif receptor 4; G-MDSC = granulocytic myeloid-derived suppressor cell; GBM = glioblastoma; M-MDSC = monocytic myeloid-derived suppressor cell; MIF = macrophage migration inhibitory factor; MCP-1 = monocyte chemoattractant protein-1; NK = natural killer cell; TPT1 = translationally controlled tumor protein-1.
See this image and copyright information in PMC

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