Macrophage migration inhibitory factor–CD74 signaling pathway (MIF–CD74) (MIF–CD74)

The Macrophage migration inhibitory factor (MIF)–CD74 signaling pathway is a pivotal regulatory axis in both the immune system and oncogenesis. MIF is a pleiotropic cytokine that, upon binding to its high-affinity cell-surface receptor CD74 (the MHC class II invariant chain), triggers a cascade of intracellular signaling events including the activation of the ERK1/2, PI3K/AKT, and NF-κB pathways (PMID: 23547090). This signaling promotes cell survival, proliferation, and the production of pro-inflammatory mediators, while simultaneously suppressing p53-mediated apoptosis. In the tumor microenvironment, the MIF–CD74 axis is often hijacked to facilitate tumor growth, promote angiogenesis, and recruit immunosuppressive myeloid-derived suppressor cells (MDSCs), thereby aiding in immune evasion (PMID: 28453534). Therapeutic targeting of this pathway involves the use of monoclonal antibodies like Milatuzumab (anti-CD74) and Imalumab (anti-MIF), as well as small molecule inhibitors like ISO-1 that block the MIF tautomerase active site required for receptor binding. Clinical applications are being explored in various B-cell malignancies, solid tumors, and chronic inflammatory diseases such as rheumatoid arthritis and systemic lupus erythematosus.

Other names

MIF/CD74 axisMIF-CD74 complexMacrophage migration inhibitory factor/HLA class II antigen-associated invariant chain axis

Neutralization of MIF cytokine activity, competitive inhibition of MIF binding to CD74, and antibody-dependent cellular cytotoxicity (ADCC) against CD74-expressing cells.