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Role of different epigenetic drugs in reshaping murine melanoma tumor microenvironment

GSE254070 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/01/31 Platform GPL24247
Summary
To highlight the role of epigenetics in immune responses, we exploited a model of melanoma using B16F10 injected subcutaneously in syngeneic C57black6j mice and studied the effect of inhibitors of (i) BET bromodomain (OTX-015) (ii) DNA methyltransferase (DNMT) (guadecitabine) on in vivo tumour growth. OTX-015 showed significant in vivo effects in reducing tumour growth in our setting. Guadecitabine induced MHC class I expression on tumour cells, but the latter also increased immune checkpoint expression on cancer cells. Each epigenetic agent altered the tumour microenvironment (TME), mostly by reducing immune suppression, particularly of Tregs or MDSC, or both. OTX-015 and guadecitabine had strong effects, but in opposite ways. OTX-015 downmodulated antitumour responses, whereas guadecitabine remodeled the TME to be more immune-responsive. Epigenetic therapy may enhance immunotherapy, but specific schedules for treatments need to be studied for each drug. Among the drugs tested, guadecitabine seems to be the most promising drug for successful combination immunotherapy.
Published in
The Systematic Comparison of Enhancer of Zeste Homolog-2-, Bromodomain-containing Proteins-, Histone Deacetylase-, and DNA-methyltransferase 1-inhibitors in a Syngeneic Murine Model of Melanoma Reveals Differential Anti-tumoral and Immunomodulatory Activities
Rigo V, Amaro A, Reggiani F et al. · MedComm 2025 · PMID 40787072 · doi:10.1002/mco2.70336
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Also filed as BioProject PRJNA1068500 and SRA study SRP485646. Searching any of these in the dataset finder brings you back here.

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