American Association for Cancer Research
23266066cir170080-sup-178782_2_supp_4083495_nr4cph.pdf (415.38 kB)

Fragale et al_Supplementary Figure S3_CIR from Antitumor Effects of Epidrug/IFNα Combination Driven by Modulated Gene Signatures in Both Colorectal Cancer and Dendritic Cells

Download (415.38 kB)
journal contribution
posted on 2023-04-03, 23:22 authored by Alessandra Fragale, Giulia Romagnoli, Valerio Licursi, Maria Buoncervello, Giorgia Del Vecchio, Caterina Giuliani, Stefania Parlato, Celeste Leone, Marta De Angelis, Irene Canini, Elena Toschi, Filippo Belardelli, Rodolfo Negri, Imerio Capone, Carlo Presutti, Lucia Gabriele

Supplementary Figure 3 Biological processes categories enriched in the list of genes showing H3K9me2 peaks in the promoter region.


Italian Association for Research against Cancer




Colorectal cancer results from the progressive accumulation of genetic and epigenetic alterations. IFN signaling defects play an important role in the carcinogenesis process, in which the inability of IFN transcription regulatory factors (IRF) to access regulatory sequences in IFN-stimulated genes (ISG) in tumors and in immune cells may be pivotal. We reported that low-dose combination of two FDA-approved epidrugs, azacytidine (A) and romidepsin (R), with IFNα2 (ARI) hampers the aggressiveness of both colorectal cancer metastatic and stem cells in vivo and triggers immunogenic cell death signals that stimulate dendritic cell (DC) function. Here, we investigated the molecular signals induced by ARI treatment and found that this drug combination increased the accessibility to regulatory sequences of ISGs and IRFs that were epigenetically silenced in both colorectal cancer cells and DCs. Likewise, specific ARI-induced histone methylation and acetylation changes marked epigenetically affected ISG promoters in both metastatic cancer cells and DCs. Analysis by ChIP-seq confirmed such ARI-induced epigenetically regulated IFN signature. The activation of this signal endowed DCs with a marked migratory capability. Our results establish a direct correlation between reexpression of silenced ISGs by epigenetic control and ARI anticancer activity and provide new knowledge for the development of innovative combined therapeutic strategies for colorectal cancer. Cancer Immunol Res; 5(7); 604–16. ©2017 AACR.