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. 2025 Aug 9;6(8):e70336.
doi: 10.1002/mco2.70336. eCollection 2025 Aug.

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

Valentina Rigo  1 , Adriana Amaro  2 , Francesco Reggiani  2 , Daniela Fenoglio  1 , Stefania Martini  3 , Tiziana Altosole  1 , Mariangela Petito  2 , Cecilia Profumo  1 , Michela Croce  1
Affiliations

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

Valentina Rigo et al. MedComm (2020). .
No abstract available

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
(A) In vivo activity of epigenetic drugs. Schedule of treatments and tumor volume growth in control (Ctrl) and mice treated with GSK‐126, vorinostat (vor), OTX‐015 (OTX), and guadecitabine (guad). N = 10 mice/group * p < 0.05, ** p < 0.01, *** p < 0.001. (B) Table embedded in the Figure shows the epigenetic drug effects on TME. Cell suspensions from control and treated tumors were analyzed by flow cytometry. Mean ± SD of percentages and p are indicated. Classical Treg are defined as CD45+CD3+CD4+CD25+Foxp3+; monocytic‐MDSC as Ly6C+Ly6G‐/CD11b+, and granulocytic‐MDSC as Ly6ClowLy6G+/CD11b+, referred to as CD11b+CD45+ cells. N = 8 mice/group have been analyzed * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001. (C) Table embedded in the Figure shows cytokine or chemokine modifications induced by epigenetic drug treatments. Serum cytokine or chemokine levels expressed in pg/mL from mice treated with vorinostat, OTX‐015, and guadecitabine. N = 8–10 mice/group data are presented as mean ± sd * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001. (D) Epigenetic drug treatment affects gene expression. Top panel (left to right): Heatmap of differentially expressed genes in tumors from: Ctrl (blue line) and guadecitabine‐treated removed 2 (green line) and 10 (light brown line) days after EOT; OTX‐015‐treated mice, collected at 2 (green line) and 7 (light brown line) days after EOT; vorinostat‐treated mice (green line). Sample size: n = 2–10 mice/group. Middle panel: Left: KEGG pathway enrichment analysis of 442 genes up‐modulated by guadecitabine, Right: Gene Ontology (GO) analysis of biological process affected in vorinostat‐treated tumors compared to controls. Bottom panel: KEGG pathway enrichment analysis of 352 down‐modulated genes by guadecitabine. Bubble plots: the horizontal axis indicates fold enrichment (Ratio of differentially expressed genes present in the GO or KEGG pathways to the total number of genes in the reference gene set), the vertical axis shows the categories from the Gene Ontology Biological Process or KEGG pathways.
See this image and copyright information in PMC

References

    1. Sun L., Zhang H., and Gao P., “Metabolic Reprogramming and Epigenetic Modifications on the Path to Cancer,” Protein Cell 13, no. 12 (2022): 877–919. - PMC - PubMed
    1. Anichini A., Molla A., Nicolini G., et al., “Landscape of Immune‐related Signatures Induced by Targeting of Different Epigenetic Regulators in Melanoma: Implications for Immunotherapy,” Journal of Experimental & Clinical Cancer Research 41, no. 1 (2022): 325. - PMC - PubMed
    1. Amaro A., Reggiani F., Fenoglio D., et al., “Guadecitabine Increases Response to Combined Anti‐CTLA‐4 and Anti‐PD‐1 Treatment in Mouse Melanoma in Vivo by Controlling T‐cells, Myeloid Derived Suppressor and NK Cells,” Journal of Experimental & Clinical Cancer Research 42, no. 1 (2023): 67. - PMC - PubMed
    1. Cheuk Y. C., Xu S., Zhu D., et al., “Monocytic Myeloid‐Derived Suppressor Cells Inhibit Myofibroblastic Differentiation in Mesenchymal Stem Cells through IL‐15 Secretion,” Frontiers in Cell and Developmental Biology 10 (2022): 817402. - PMC - PubMed
    1. Banchereau J. and Steinman R. M., “Dendritic Cells and the Control of Immunity,” Nature 392, no. 6673 (1998): 245–252. - PubMed