Inhibition of EZH2 methyltransferase decreases immunoediting of mesothelioma cells by autologous macrophages through a PD-1–dependent mechanism

Hamaïdia, Malik; Gazon, Hélène; Hoyos, Clotilde; Hoffmann, Gabriela Brunsting; Louis, Renaud; Duysinx, Bernard; Willems, Luc

doi:10.1172/jci.insight.128474

Cited by 41 publications

(44 citation statements)

References 45 publications

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“…Enhancer of zeste homolog 2 (EZH2) is a histone H3 lysine 27‐specific methyltransferase (H3K27me) of the polycomb repressive complex 2 (PRC2) 16 . EZH2 is highly expressed in various cancers, such as breast cancer 17 and ovarian cancer 18,19 .…”

Section: Introductionmentioning

confidence: 99%

“…15 Enhancer of zeste homolog 2 (EZH2) is a histone H3 lysine 27-specific methyltransferase (H3K27me) of the polycomb repressive complex 2 (PRC2). 16 EZH2 is highly expressed in various cancers, such as breast cancer 17 and ovarian cancer. 18,19 High expression of EZH2 in OC promoted cell proliferation and correlated with a high proliferative index and tumour grade in OC.…”

Section: Introductionmentioning

confidence: 99%

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Long noncoding RNA ATB promotes ovarian cancer tumorigenesis by mediating histone H3 lysine 27 trimethylation through binding to EZH2

Chen

2020

J Cellular Molecular Medi

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA ATB promotes ovarian cancer tumorigenesis by mediating histone H3 lysine 27 trimethylation through binding to EZH2

Chen

2020

J Cellular Molecular Medi

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“…This is the first demonstration that PD-1 expression has a significant role in macrophages 20 . In malignant pleural mesothelioma, macrophages have a direct cytotoxic effect on mesothelioma cells, which is not related to phagocytosis 52 . However, this activity is weakened when PD-1 is overexpressed 52 .…”

Section: Effects Of Immune Cells With High Expression Of Pd-1 or Pd-lmentioning

confidence: 92%

“…In malignant pleural mesothelioma, macrophages have a direct cytotoxic effect on mesothelioma cells, which is not related to phagocytosis 52 . However, this activity is weakened when PD-1 is overexpressed 52 . PD-1 blockade restores macrophage-dependent cytotoxicity and antitumor activity 52 .…”

Section: Effects Of Immune Cells With High Expression Of Pd-1 or Pd-lmentioning

confidence: 92%

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Comprehensive insights into the effects and regulatory mechanisms of immune cells expressing programmed death-1/programmed death ligand 1 in solid tumors

et al. 2020

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Histone methyltransferase Ezh2 negatively regulates NK cell terminal maturation and function

Huang

et al. 2021

Journal of Leukocyte Biology

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NK cells are innate lymphoid cells that play important roles in tumor eradication and viral clearance. We previously found that deletion or inhibition of the histone methyltransferase Ezh2 (enhancer of zeste homolog 2) in hematopoietic stem and progenitor cells (HSPCs) from both mice and humans enhanced the commitment and cytotoxicity of NK cells to tumor cells. This study tested the hypothesis that inhibiting Ezh2, especially in NK lineage cells, could also affect NK cell development and function. We crossed Ezh2fl/fl mice with Ncr1iCre mice to delete the Ezh2 gene in immature NK cells and downstream progeny. Ezh2 deficiency increased the total number of NK cells and promoted NK cell terminal differentiation, as the percentages of the most mature CD27–CD11b+ subsets were increased. The NK cell cytotoxicity against tumor cells in vitro was enhanced, with increased degranulation and IFN‐γ production. In addition, during the process of human NK cells differentiating from HSPCs , inhibiting EZH2 catalytic activity at day 14 (when NK lineage commitment began) also resulted in increased proportions of mature NK cells and cytotoxicity. Furthermore, RNA‐seq and CUT&RUN‐qPCR assays showed that the effects of Ezh2 may be based on its direct modulation of the expression of the transcription factor Pbx1 (pre‐B‐cell leukemia transcription factor 1), which has been reported to promote NK cell development. In summary, we demonstrate that Ezh2 is a negative regulator of NK cell terminal maturation and function.

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Inhibition of EZH2 methyltransferase decreases immunoediting of mesothelioma cells by autologous macrophages through a PD-1–dependent mechanism

Cited by 41 publications

References 45 publications

Long noncoding RNA ATB promotes ovarian cancer tumorigenesis by mediating histone H3 lysine 27 trimethylation through binding to EZH2

Long noncoding RNA ATB promotes ovarian cancer tumorigenesis by mediating histone H3 lysine 27 trimethylation through binding to EZH2

Comprehensive insights into the effects and regulatory mechanisms of immune cells expressing programmed death-1/programmed death ligand 1 in solid tumors

Histone methyltransferase Ezh2 negatively regulates NK cell terminal maturation and function

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