ArticleInternational journal of molecular sciences2021
Inhibition of the Histone Methyltransferase EZH2 Enhances Protumor Monocyte Recruitment in Human Mesothelioma Spheroids.
Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- Model-dependent GD2 upregulation in Ewing sarcoma with the EZH2 inhibitor tazemetostat: Prerequisites for combination with GD2-specific CAR T cells.Research square · 2026Article
- Review
- EZH2 Inhibition in Mesothelioma Cells Increases the Release of Extracellular Vesicles That Skew Neutrophils Toward a Protumor Phenotype.International journal of molecular sciences · 2025Article
- Review
- Highlighting recent achievements to advance more effective cancer immunotherapy.Journal of experimental & clinical cancer research : CR · 2025Article
- Review
- Less Severe Sepsis in Cecal Ligation and Puncture Models with and without Lipopolysaccharide in Mice with ConditionalInternational journal of molecular sciences · 2023Article
- The Regulatory Roles ofInternational journal of molecular sciences · 2023Article
- Review
- Excess of blood eosinophils prior to therapy correlates with worse prognosis in mesothelioma.Frontiers in immunology · 2023Article
- Immune activation is essential for the antitumor activity of EZH2 inhibition in urothelial carcinoma.Science advances · 2022Article
- Analysis of the correlation between Zeste enhancer homolog 2 (EZH2) mRNA expression and the prognosis of mesothelioma patients and immune infiltration.Scientific reports · 2022Article
- Regulation of CCL2 by EZH2 affects tumor-associated macrophages polarization and infiltration in breast cancer.Cell death & disease · 2022Article
- HDAC Inhibition with Valproate Improves Direct Cytotoxicity of Monocytes against Mesothelioma Tumor Cells.Cancers · 2022Article
- Evolution and Targeting of Myeloid Suppressor Cells in Cancer: A Translational Perspective.Cancers · 2022Review
- EZH2 Inhibitors Suppress Colorectal Cancer by Regulating Macrophage Polarization in the Tumor Microenvironment.Frontiers in immunology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Malignant pleural mesothelioma (MPM) is a highly aggressive cancer with a long latency period and dismal prognosis. Recently, tazemetostat (EPZ-6438), an inhibitor of the histone methyltransferase EZH2, has entered clinical trials due to the antiproliferative effects reported on MPM cells. However, the direct and indirect effects of epigenetic reprogramming on the tumor microenvironment are hitherto unexplored. To investigate the impact of tumor-associated macrophages (TAMs) on MPM cell responsiveness to tazemetostat, we developed a three-dimensional MPM spheroid model that recapitulates in vitro, both monocytes' recruitment in tumors and their functional differentiation toward a TAM-like phenotype (Mo-TAMs). Along with an increased expression of genes for monocyte chemoattractants, inhibitory immune checkpoints, immunosuppressive and M2-like molecules, Mo-TAMs promote tumor cell proliferation and spreading. Prolonged treatment of MPM spheroids with tazemetostat enhances both the recruitment of Mo-TAMs and the expression of their protumor phenotype. Therefore, Mo-TAMs profoundly suppress the antiproliferative effects due to EZH2 inhibition in MPM cells. Overall, our findings indicate that TAMs are a driving force for MPM growth, progression, and resistance to tazemetostat; therefore, strategies of TAM depletion might be evaluated to improve the therapeutic efficacy of pharmacological inhibition of EZH2.
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