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Here, we have explored the effects of a novel histone deacetylase (HDAC) inhibitor CM-1758, alone or in combination with immune checkpoint inhibitors (ICI) in BC. We determined the antitumor effects of CM-1758 in various BC cell lines together with the induction of broad transcriptional changes, with focus on the epigenetic regulation of PD-L1. Using an immunocompetent syngeneic mouse model of metastatic BC, we studied the effects of CM-1758 alone or in combination with anti-PD-L1 not only on tumor cells, but also in the tumor microenvironment. In vitro, we found that CM-1758 has cytotoxic and cytostatic effects either by inducing apoptosis or cell cycle arrest in BC cells at low micromolar levels. PD-L1 is epigenetically regulated by histone acetylation marks and is induced after treatment with CM-1758. We also observed that treatment with CM-1758 led to an important delay in tumor growth and a higher CD8\u2009+\u2009T cell tumor infiltration. Moreover, anti-PD-L1 alone or in combination with CM-1758 reprogramed macrophage differentiation towards a M1-like polarization state and increased of pro-inflammatory cytokines systemically, yielding potential further antitumor effects. Our results suggest the possibility of combining HDAC inhibitors with immunotherapies for the management of advanced metastatic BC.<\/jats:p>","DOI":"10.1038\/s41420-023-01786-3","type":"journal-article","created":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T05:00:49Z","timestamp":1704344449000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Modulation of tumor microenvironment by targeting histone acetylation in bladder cancer"],"prefix":"10.1038","volume":"10","author":[{"given":"Sandra P.","family":"Nunes","sequence":"first","affiliation":[]},{"given":"Lucia","family":"Morales","sequence":"additional","affiliation":[]},{"given":"Carolina","family":"Rubio","sequence":"additional","affiliation":[]},{"given":"Ester","family":"Munera-Maravilla","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5208-8249","authenticated-orcid":false,"given":"Iris","family":"Lodewijk","sequence":"additional","affiliation":[]},{"given":"Cristian","family":"Su\u00e1rez-Cabrera","sequence":"additional","affiliation":[]},{"given":"Victor G.","family":"Mart\u00ednez","sequence":"additional","affiliation":[]},{"given":"Mercedes","family":"P\u00e9rez-Escavy","sequence":"additional","affiliation":[]},{"given":"Miriam","family":"P\u00e9rez-Crespo","sequence":"additional","affiliation":[]},{"given":"Miguel","family":"Alonso S\u00e1nchez","sequence":"additional","affiliation":[]},{"given":"Esther","family":"Montesinos","sequence":"additional","affiliation":[]},{"given":"Edurne","family":"San Jos\u00e9-En\u00e9riz","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6558-9560","authenticated-orcid":false,"given":"Xabier","family":"Agirre","sequence":"additional","affiliation":[]},{"given":"Felipe","family":"Pr\u00f3sper","sequence":"additional","affiliation":[]},{"given":"Antonio","family":"Pineda-Lucena","sequence":"additional","affiliation":[]},{"given":"Rui","family":"Henrique","sequence":"additional","affiliation":[]},{"given":"Marta","family":"Due\u00f1as","sequence":"additional","affiliation":[]},{"given":"Margareta P.","family":"Correia","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4186-5345","authenticated-orcid":false,"given":"Carmen","family":"Jer\u00f3nimo","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7520-3177","authenticated-orcid":false,"given":"Jes\u00fas M.","family":"Paramio","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2024,1,4]]},"reference":[{"key":"1786_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. 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