# MIF as an oncogenic driver of low‐heterogeneity melanomas

## TL;DR

This paper shows that MIF, a cytokine, drives tumor growth and immune resistance in melanomas with low diversity.

## Contribution

The study identifies MIF as a key oncogenic driver in low-heterogeneity melanomas and suggests its inhibition as a therapeutic strategy.

## Key findings

- MIF is upregulated in melanomas with low intratumoral heterogeneity and mediates immune resistance.
- MIF contributes to an immunosuppressive tumor microenvironment by suppressing T cells and promoting tumor-permissive macrophages.

## Abstract

Identifying targets involved in tumor evolution and immune escape is an active area of research in oncology. Macrophage migration inhibitory factor (MIF) is an upstream immunoregulatory cytokine that promotes transformed cell proliferation and survival, and generates a tumor‐permissive immune landscape of immunosuppressive myeloid and T cells. Shvefel and colleagues have identified a key role for MIF in tumor progression in melanoma clones with low tumor heterogeneity. These findings provide important insights into the potential therapeutic utility of MIF antagonists and support ongoing research to utilize MIF pathway inhibitors for improved therapeutic outcomes.

Shvefel and colleagues identified tumor‐secreted macrophage migration inhibitory factor (MIF) as an upregulated cytokine that mediates immune resistance in melanomas with low‐intratumoral heterogeneity. MIF and its functional paralogue D‐dopachrome tautomerase (D‐DT or MIF‐2) have overlapping but nonidentical signaling functions and are hypothesized to generate immune suppressive tumor microenvironments characterized by T‐cell suppression and tumor‐permissive macrophage populations.