MIF-Dependent Control of Tumor Immunity

Initially identified as a T lymphocyte-elicited inhibitor of macrophage motility, macrophage migration inhibitory factor (MIF) has since been found to be expressed by nearly every immune cell type examined and over-expressed in most solid and hematogenous malignant cancers. It is localized to both extracellular and intracellular compartments and physically interacts with more than a dozen different cell surface and intracellular proteins. Although classically associated with and characterized as a mediator of pro-inflammatory innate immune responses, more recent studies demonstrate that, in malignant disease settings, MIF promotes anti-inflammatory, immune evasive and immune tolerant phenotypes in both innate and adaptive immune cell types. This review will summarize the studies describing MIF in tumor-specific innate and adaptive immune responses and attempt to reconcile these various pleotropic functions in normal physiology.