Oncotarget #published this #trending research #paper on July 19, 2024 in Volume 15, entitled, “Prognostic and therapeutic insights into MIF, DDT, and CD74 in melanoma” by researchers from School of Medicine, Yale University, New Haven, CT; Department of Medicine, Section of Rheumatology, Allergy and Immunology, Yale University, New Haven, CT; Department of Dermatology, Yale University, New Haven, CT; Department of Dermatology, Oregon Health and Science University, Portland, OR; Cancer Early Detection Advanced Research Center (CEDAR), Portland, OR; Knight Cancer Institute, Oregon Health and Science University, Portland, OR; Department of Veterans Affairs Portland Health Care System, Operative Care Division, U.S. Portland, OR; Department of Medicine, Section of Medical Oncology, Yale University, New Haven, CT; Yale Cancer Center, Yale University, New Haven, CT. @YaleSchoolOfMedicine
#cancer #melanoma #skincancer #research #openaccess #openscience #peerreview #journal #publication #publishing #meded
DOI - doi.org/10.186...
Correspondence to - Thuy Tran - thuy.tran@yale.edu
Abstract
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. This retrospective study analyzed 97 patients treated at Yale for melanoma between 2002-2020. 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. Our 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.
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Keywords - cancer, MIF, DDT, melanoma, immune checkpoint inhibition, cancer transcriptomics
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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.
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