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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Immunological Effects of Epigenetic Modifiers
Lucillia Bezu1,2,3,4,5, Alejandra Wu Chuang2,3,4,5, Peng Liu3,4,5
1Service anesthésie-réanimation, Hôpital européen Georges Pompidou, AP-HP, 75015 Paris, France.
Abstract:
Epigenetic alterations are associated with major pathologies including cancer. Epigenetic dysregulation, such as aberrant histone acetylation, altered DNA methylation, or modified chromatin organization, contribute to oncogenesis by inactivating tumor suppressor genes and activating oncogenic pathways. Targeting epigenetic cancer hallmarks can be harnessed as an immunotherapeutic strategy, exemplified by the use of pharmacological inhibitors of DNA methyltransferases (DNMT) and histone deacetylases (HDAC) that can result in the release from the tumor of danger-associated molecular patterns (DAMPs) on one hand and can (re-)activate the expression of tumor-associated antigens on the other hand. This finding suggests that epigenetic modifiers and more specifically the DNA methylation status may change the interaction of chromatin with chaperon proteins including HMGB1, thereby contributing to the antitumor immune response. In this review, we detail how epigenetic modifiers can be used for stimulating therapeutically relevant anticancer immunity when used as stand-alone treatments or in combination with established immunotherapies.
Insights
Epigenetic modifiers like DNA methyltransferase (DNMT) and histone deacetylase (HDAC) inhibitors can enhance anticancer immunity. These epigenetic drugs can stimulate anti-tumor immune responses by releasing danger signals and re-activating tumor antigens.
Area of Science:
- Oncology
- Immunology
- Epigenetics
Background:
- Epigenetic alterations, including histone acetylation and DNA methylation changes, are hallmarks of cancer.
- These epigenetic dysregulations contribute to oncogenesis by affecting tumor suppressor genes and oncogenic pathways.
Purpose of the Study:
- To review how epigenetic modifiers can be utilized to stimulate anticancer immunity.
- To explore the potential of epigenetic drugs as standalone or combination therapies for cancer immunotherapy.
Main Methods:
- Review of literature on epigenetic alterations in cancer.
- Analysis of the mechanisms by which epigenetic modifiers influence the tumor microenvironment and immune response.
- Examination of the role of DNA methylation and chromatin interactions with proteins like HMGB1.
Main Results:
- Pharmacological inhibitors of DNA methyltransferases (DNMT) and histone deacetylases (HDAC) can trigger anti-tumor immunity.
- Epigenetic therapies can lead to the release of danger-associated molecular patterns (DAMPs) from tumors.
- These treatments can also re-activate the expression of tumor-associated antigens, enhancing immune recognition.
Conclusions:
- Epigenetic modifiers represent a promising strategy for stimulating therapeutically relevant anticancer immunity.
- Targeting epigenetic cancer hallmarks offers a novel approach for standalone or combination immunotherapies.
- Modulating DNA methylation status can significantly impact chromatin interactions and bolster anti-tumor immune responses.
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