Role of Epigenetic Modifications in Inhibitory Immune Checkpoints in Cancer Development and Progression
<p dir="ltr">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 pr...
محفوظ في:
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| مؤلفون آخرون: | , , |
| منشور في: |
2020
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| الموضوعات: | |
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إضافة وسم
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| _version_ | 1864513512263385088 |
|---|---|
| author | Reem Saleh (3513056) |
| author2 | Salman M. Toor (8854751) Varun Sasidharan Nair (5396393) Eyad Elkord (5396390) |
| author2_role | author author author |
| author_facet | Reem Saleh (3513056) Salman M. Toor (8854751) Varun Sasidharan Nair (5396393) Eyad Elkord (5396390) |
| author_role | author |
| dc.creator.none.fl_str_mv | Reem Saleh (3513056) Salman M. Toor (8854751) Varun Sasidharan Nair (5396393) Eyad Elkord (5396390) |
| dc.date.none.fl_str_mv | 2020-07-14T06:00:00Z |
| dc.identifier.none.fl_str_mv | 10.3389/fimmu.2020.01469 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Role_of_Epigenetic_Modifications_in_Inhibitory_Immune_Checkpoints_in_Cancer_Development_and_Progression/26114434 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Genetics Biomedical and clinical sciences Oncology and carcinogenesis cancer immune checkpoints epigenetics DNA methylation histone modifications therapeutic targets |
| dc.title.none.fl_str_mv | Role of Epigenetic Modifications in Inhibitory Immune Checkpoints in Cancer Development and Progression |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Immunology<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fimmu.2020.01469" target="_blank">https://dx.doi.org/10.3389/fimmu.2020.01469</a></p><p dir="ltr"><br></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_ec51a0d298dfa298dd4a59229babdd82 |
| identifier_str_mv | 10.3389/fimmu.2020.01469 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26114434 |
| publishDate | 2020 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Role of Epigenetic Modifications in Inhibitory Immune Checkpoints in Cancer Development and ProgressionReem Saleh (3513056)Salman M. Toor (8854751)Varun Sasidharan Nair (5396393)Eyad Elkord (5396390)Biological sciencesBiochemistry and cell biologyGeneticsBiomedical and clinical sciencesOncology and carcinogenesiscancerimmune checkpointsepigeneticsDNA methylationhistone modificationstherapeutic targets<p dir="ltr">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.</p><h2>Other Information</h2><p dir="ltr">Published in: Frontiers in Immunology<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3389/fimmu.2020.01469" target="_blank">https://dx.doi.org/10.3389/fimmu.2020.01469</a></p><p dir="ltr"><br></p>2020-07-14T06:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3389/fimmu.2020.01469https://figshare.com/articles/journal_contribution/Role_of_Epigenetic_Modifications_in_Inhibitory_Immune_Checkpoints_in_Cancer_Development_and_Progression/26114434CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/261144342020-07-14T06:00:00Z |
| spellingShingle | Role of Epigenetic Modifications in Inhibitory Immune Checkpoints in Cancer Development and Progression Reem Saleh (3513056) Biological sciences Biochemistry and cell biology Genetics Biomedical and clinical sciences Oncology and carcinogenesis cancer immune checkpoints epigenetics DNA methylation histone modifications therapeutic targets |
| status_str | publishedVersion |
| title | Role of Epigenetic Modifications in Inhibitory Immune Checkpoints in Cancer Development and Progression |
| title_full | Role of Epigenetic Modifications in Inhibitory Immune Checkpoints in Cancer Development and Progression |
| title_fullStr | Role of Epigenetic Modifications in Inhibitory Immune Checkpoints in Cancer Development and Progression |
| title_full_unstemmed | Role of Epigenetic Modifications in Inhibitory Immune Checkpoints in Cancer Development and Progression |
| title_short | Role of Epigenetic Modifications in Inhibitory Immune Checkpoints in Cancer Development and Progression |
| title_sort | Role of Epigenetic Modifications in Inhibitory Immune Checkpoints in Cancer Development and Progression |
| topic | Biological sciences Biochemistry and cell biology Genetics Biomedical and clinical sciences Oncology and carcinogenesis cancer immune checkpoints epigenetics DNA methylation histone modifications therapeutic targets |