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The Cancer Epigenome: Exploiting Its Vulnerabilities for Immunotherapy
Helen Loo Yau1, Ilias Ettayebi1, Daniel D De Carvalho1
1Princess Margaret Cancer Centre, University Health Network, Toronto, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Canada.
Abstract:
During cancer initiation and progression, the somatic epigenome is broadly reprogrammed. This reprogramming can be a consequence of several processes, including altered transcriptional profiles and mutations. In addition, immune cells infiltrating the tumor microenvironment display a reprogrammed epigenome. For instance, tumor infiltrating T cells frequently exhibit an exhausted phenotype characterized by aberrant DNA methylation. Moreover, these aberrant epigenomes of cancer cells and infiltrating immune cells may represent a cancer vulnerability. Accumulating evidence supports the potential of using epigenetic therapy to not only reactivate silenced genes in cancer cells, but to also increase antitumor immunogenicity, by reactivation of endogenous retroviruses, to increase tumor immune-infiltration, and to reinvigorate T cell exhaustion. These findings highlight the potential synergies between epigenetic therapies and immunotherapy.
Insights
Cancer cells and immune cells undergo epigenetic reprogramming, creating vulnerabilities. Epigenetic therapy can exploit these changes to enhance cancer immunotherapy by reinvigorating T cells and increasing tumor immunogenicity.
Area of Science:
- Oncology
- Immunology
- Epigenetics
Background:
- Cancer progression involves broad epigenetic reprogramming in tumor cells and infiltrating immune cells.
- Tumor-infiltrating T cells often display an exhausted phenotype linked to aberrant DNA methylation.
- These epigenetic alterations in cancer and immune cells represent potential therapeutic vulnerabilities.
Purpose of the Study:
- To explore the potential of epigenetic therapy in cancer treatment.
- To investigate how epigenetic reprogramming can be leveraged to enhance antitumor immunity.
- To examine the synergy between epigenetic therapies and immunotherapy.
Main Methods:
- Analysis of somatic epigenome reprogramming during cancer initiation and progression.
- Characterization of epigenetic changes in tumor-infiltrating immune cells, particularly T cells.
- Review of evidence supporting epigenetic therapy's role in modulating cancer cell gene expression and immune responses.
Main Results:
- Aberrant epigenomes in cancer cells and immune cells present a vulnerability.
- Epigenetic therapy can reactivate silenced genes in cancer cells.
- Epigenetic therapy shows potential to increase antitumor immunogenicity and reinvigorate exhausted T cells.
Conclusions:
- Epigenetic reprogramming in the tumor microenvironment offers therapeutic targets.
- Epigenetic therapies hold promise for enhancing cancer immunotherapy outcomes.
- Synergistic effects between epigenetic agents and immunotherapies warrant further investigation.
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