دورية أكاديمية
Dual G9A/EZH2 inhibition stimulates anti-tumour immune response in ovarian high grade serous carcinoma
| العنوان: | Dual G9A/EZH2 inhibition stimulates anti-tumour immune response in ovarian high grade serous carcinoma |
|---|---|
| المؤلفون: | Spiliopoulou, Pavlina, Spear, Sarah, Mirza, Hasan, Garner, Ian, Iyer, Nayana, McGarry, Lynn, Grundland-Freile, Fabio, Cheng, Zhao, Ennis, Darren P., McNamara, Sophie, Natoli, Marina, Mason, Susan, Blyth, Karen, Adams, Peter D., Roxburgh, Patricia, Fuchter, Matthew J., Brown, Bob, McNeish, Iain A. |
| بيانات النشر: | American Association for Cancer Research |
| سنة النشر: | 2022 |
| المجموعة: | University of Glasgow: Enlighten - Publications |
| الوصف: | Ovarian high-grade serous carcinoma (HGSC) prognosis correlates directly with presence of intratumoral lymphocytes. However, cancer immunotherapy has yet to achieve meaningful survival benefit in patients with HGSC. Epigenetic silencing of immunostimulatory genes is implicated in immune evasion in HGSC and re-expression of these genes could promote tumour immune clearance. We discovered that simultaneous inhibition of the histone methyltransferases G9A and EZH2 activates the CXCL10-CXCR3 axis and increases homing of intratumoral effector lymphocytes and natural killer cells whilst suppressing tumour-promoting FoxP3+ CD4 T cells. The dual G9A/EZH2 inhibitor HKMTI-1-005 induced chromatin changes that resulted in the transcriptional activation of immunostimulatory gene networks, including the re-expression of elements of the ERV-K endogenous retroviral family. Importantly, treatment with HKMTI-1-005 improved the survival of mice bearing Trp53-/- null ID8 ovarian tumours and resulted in tumour burden reduction. These results indicate that inhibiting G9A and EZH2 in ovarian cancer alters the immune microenvironment and reduces tumour growth and therefore positions dual inhibition of G9A/EZH2 as a strategy for clinical development. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | text |
| اللغة: | English |
| العلاقة: | https://eprints.gla.ac.uk/264916/1/264916.pdfTest; Spiliopoulou, P. et al. (2022) Dual G9A/EZH2 inhibition stimulates anti-tumour immune response in ovarian high grade serous carcinoma. Molecular Cancer Therapeutics , 21(4), pp. 522-534. (doi:10.1158/1535-7163.MCT-21-0743 ) (PMID:35131874) (PMCID:PMC9377747) |
| الإتاحة: | https://doi.org/10.1158/1535-7163.MCT-21-0743Test https://eprints.gla.ac.uk/264916Test/ https://eprints.gla.ac.uk/264916/1/264916.pdfTest |
| حقوق: | cc_by_4 |
| رقم الانضمام: | edsbas.7D7FF7DD |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |