Role of epigenetic modifications in inhibitory immune checkpoints in cancer development and progression

Saleh, R, Toor, SM, Sasidharan Nair, V and Elkord, E 2020, 'Role of epigenetic modifications in inhibitory immune checkpoints in cancer development and progression' , Frontiers in Immunology, 11 , p. 1469.

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Abstract

A balance between co-inhibitory and co-stimulatory signals in the tumor microenvironment (TME) is critical to suppress tumor development and progression, primarily via maintaining effective immunosurveillance. Aberrant expression of immune checkpoints (ICs), including programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), lymphocyte-activation gene 3 (LAG-3) and T cell immunoreceptor with Ig and ITIM domains (TIGIT), can create an immune-subversive environment, which helps tumor cells to evade immune destruction. Recent studies showed that epigenetic modifications play critical roles in regulating the expression of ICs and their ligands in the TME. Reports showed that the promoter regions of genes encoding ICs/IC ligands can undergo inherent epigenetic alterations, such as DNA methylation and histone modifications (acetylation and methylation). These epigenetic aberrations can significantly contribute to the transcriptomic upregulation of ICs and their ligands. Epigenetic therapeutics, including DNA methyltransferase and histone deacetylase inhibitors, can be used to revert these epigenetic anomalies acquired during the progression of disease. These discoveries have established a promising therapeutic modality utilizing the combination of epigenetic and immunotherapeutic agents to restore the physiological epigenetic profile and to re-establish potent host immunosurveillance mechanisms. In this review, we highlight the roles of epigenetic modifications on the upregulation of ICs, focusing on tumor development, and progression. We discuss therapeutic approaches of epigenetic modifiers, including clinical trials in various cancer settings and their impact on current and future anti-cancer therapies.

Item Type: Article
Additional Information: ** From Frontiers via Jisc Publications Router ** Licence for this article: http://creativecommons.org/licenses/by/4.0/ **Journal IDs: eissn 1664-3224 **History: published_online 14-07-2020; accepted 05-06-2020; submitted 22-03-2020; collection 2020
Schools: Schools > School of Environment and Life Sciences
Journal or Publication Title: Frontiers in Immunology
Publisher: Frontiers Media S.A.
ISSN: 1664-3224
Related URLs:
Funders: Qatar Biomedical Research Institute, Qatar Foundation
SWORD Depositor: Publications Router
Depositing User: Publications Router
Date Deposited: 04 Aug 2020 12:39
Last Modified: 04 Aug 2020 12:45
URI: http://usir.salford.ac.uk/id/eprint/57725

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