ArticleJCI insight2019
Inhibition of EZH2 methyltransferase decreases immunoediting of mesothelioma cells by autologous macrophages through a PD-1-dependent mechanism.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- Antibody-lectin chimeras for glyco-immune checkpoint blockade.Nature biotechnology · 2026Article
- Metabolic-epigenetic crosstalk in innate immune cell plasticity within the tumor microenvironment.Experimental & molecular medicine · 2026Review
- Review
- Enhancer zeste homolog 2 (EZH2) targeting by small interfering RNA (siRNA); recent advances and prospect.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Selective inhibition of DNA ligase IV provides additional efficacy to the treatment of anaplastic thyroid cancer.Frontiers in oncology · 2024Article
- Targeting oxeiptosis-mediated tumor suppression: a novel approach to treat colorectal cancers by sanguinarine.Cell death discovery · 2023Article
- Review
- Inhibition of EZH2 Causes Retrotransposon Derepression and Immune Activation in Porcine Lung Alveolar Macrophages.International journal of molecular sciences · 2023Article
- Excess of blood eosinophils prior to therapy correlates with worse prognosis in mesothelioma.Frontiers in immunology · 2023Article
- Immunotherapy of mesothelioma: the evolving change of a long-standing therapeutic dream.Frontiers in immunology · 2023Review
- Analysis of the correlation between Zeste enhancer homolog 2 (EZH2) mRNA expression and the prognosis of mesothelioma patients and immune infiltration.Scientific reports · 2022Article
- Macrophages Are a Double-Edged Sword: Molecular Crosstalk between Tumor-Associated Macrophages and Cancer Stem Cells.Biomolecules · 2022Review
- HDAC Inhibition with Valproate Improves Direct Cytotoxicity of Monocytes against Mesothelioma Tumor Cells.Cancers · 2022Article
- Epigenetic Modification of PD-1/PD-L1-Mediated Cancer Immunotherapy against Melanoma.International journal of molecular sciences · 2022Review
- Evolution and Targeting of Myeloid Suppressor Cells in Cancer: A Translational Perspective.Cancers · 2022Review
- Novel Insights Into Mesothelioma Therapy: Emerging Avenues and Future Prospects.Frontiers in oncology · 2022Review
- Noncanonical PD-1/PD-L1 Axis in Relation to the Efficacy of Anti-PD Therapy.Frontiers in immunology · 2022Review
- ACVR1Bone · 2021Article
- Review
- Matter of TIME: the tumor-immune microenvironment of mesothelioma and implications for checkpoint blockade efficacy.Journal for immunotherapy of cancer · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The roles of macrophages in orchestrating innate immunity through phagocytosis and T lymphocyte activation have been extensively investigated. Much less understood is the unexpected role of macrophages in direct tumor regression. Tumoricidal macrophages can indeed manifest cancer immunoediting activity in the absence of adaptive immunity. We investigated direct macrophage cytotoxicity in malignant pleural mesothelioma, a lethal cancer that develops from mesothelial cells of the pleural cavity after occupational asbestos exposure. In particular, we analyzed the cytotoxic activity of mouse RAW264.7 macrophages upon cell-cell contact with autologous AB1/AB12 mesothelioma cells. We show that macrophages killed mesothelioma cells by oxeiptosis via a mechanism involving enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27-specific (H3K27-specific) methyltransferase of the polycomb repressive complex 2 (PRC2). A selective inhibitor of EZH2 indeed impaired RAW264.7-directed cytotoxicity and concomitantly stimulated the PD-1 immune checkpoint. In the immunocompetent BALB/c model, RAW264.7 macrophages pretreated with the EZH2 inhibitor failed to control tumor growth of AB1 and AB12 mesothelioma cells. Blockade of PD-1 engagement restored macrophage-dependent antitumor activity. We conclude that macrophages can be directly cytotoxic for mesothelioma cells independent of phagocytosis. Inhibition of the PRC2 EZH2 methyltransferase reduces this activity because of PD-1 overexpression. Combination of PD-1 blockade and EZH2 inhibition restores macrophage cytotoxicity.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.