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Prognostic and Therapeutic Insights on MIF, DDT, and CD74 in Melanoma
FOR IMMEDIATE RELEASE 2024-07-26
“[...] we present the first study to retrospectively evaluate differential gene expression of MIF, DDT, and relevant pathway markers in regard to clinical outcomes in patients with melanoma.”
Macrophage Migration Inhibitory Factor (MIF) and its homolog D-dopachrome Tautomerase (DDT) have been implicated as drivers of tumor progression across a variety of cancers. Recent evidence suggests MIF as a therapeutic target in immune checkpoint inhibition (ICI) resistant melanomas, however clinical evidence of MIF and particularly of DDT remain limited.
“Our study significantly expands on prior work by De Azevedo et al. by encompassing a larger cohort of individuals, coupled with a comprehensive approach to defining high and low MIF and DDT expression.”
Bulk-RNA sequencing of patient tumor samples from the Skin Cancer SPORE Biorepository was used to evaluate for differential gene expression of MIF, DDT, CD74, and selected inflammatory markers, and gene expression was correlated with patient survival outcomes. Their findings revealed a strong correlation between MIF and DDT levels, with no statistically significant difference across common melanoma mutations and subtypes.
Improved survival was associated with lower MIF and DDT levels and higher CD74:MIF and CD74:DDT levels. High CD74:DDT and CD74:MIF levels were also associated with enrichment of infiltrating inflammatory cell markers. These data suggest DDT as a novel target in immune therapy. Dual MIF and DDT blockade may provide synergistic responses in patients with melanoma, irrespective of common mutations, and may overcome ICI resistance. These markers may also provide prognostic value for further biomarker development.
“Our study is the first to report survival findings in association with intratumor DDT expression and CD74:DDT expression level ratio. Thus, CD74:MIF and CD74:DDT expression ratio measurements offer promise as prognostic markers for survival outcomes and ICI response in patients with melanoma.”
Keywords: MIF, DDT, melanoma, immune checkpoint inhibition, cancer transcriptomics
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About Oncotarget: Oncotarget (a primarily oncology-focused, peer-reviewed, open-access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.
Oncotarget is indexed and archived byPubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
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