Academic Journal
Modulation of tumor microenvironment by targeting histone acetylation in bladder cancer
| العنوان: | Modulation of tumor microenvironment by targeting histone acetylation in bladder cancer |
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| المؤلفون: | Sandra P. Nunes, Lucia Morales, Carolina Rubio, Ester Munera-Maravilla, Iris Lodewijk, Cristian Suárez-Cabrera, Victor G. Martínez, Mercedes Pérez-Escavy, Miriam Pérez-Crespo, Miguel Alonso Sánchez, Esther Montesinos, Edurne San José-Enériz, Xabier Agirre, Felipe Prósper, Antonio Pineda-Lucena, Rui Henrique, Marta Dueñas, Margareta P. Correia, Carmen Jerónimo, Jesús M. Paramio |
| المصدر: | Cell Death Discovery, Vol 10, Iss 1, Pp 1-15 (2024) |
| بيانات النشر: | Nature Publishing Group |
| سنة النشر: | 2024 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671 |
| الوصف: | Alterations in the epigenetic machinery in both tumor and immune cells contribute to bladder cancer (BC) development, constituting a promising target as an alternative therapeutic option. 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 + T 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2058-7716 |
| Relation: | https://doi.org/10.1038/s41420-023-01786-3; https://doaj.org/toc/2058-7716; https://doaj.org/article/2e7cebeed11f4705be37c46da8ae9498 |
| DOI: | 10.1038/s41420-023-01786-3 |
| الاتاحة: | https://doi.org/10.1038/s41420-023-01786-3 https://doaj.org/article/2e7cebeed11f4705be37c46da8ae9498 |
| رقم الانضمام: | edsbas.73A54DE2 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20587716 |
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| DOI: | 10.1038/s41420-023-01786-3 |