Journal
NATURE REVIEWS CANCER
Volume 19, Issue 3, Pages 151-161Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41568-019-0109-9
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Funding
- National Cancer Institute [R35CA209859]
- Van Andel Research Institute through the Van Andel Research Institute - Stand Up To Cancer Epigenetics Dream Team
- Canadian Institutes of Health Research (CIHR) New Investigator Salary Award [201512MSH-360794-228629]
- Princess Margaret Cancer Foundation
- CIHR Foundation [FDN 148430]
- Ontario Institute for Cancer Research (OICR)
- province of Ontario
- Guglietti Fellowship in Tumour Immune Therapy from the Princess Margaret Cancer Foundation
- Canada Research Chair [950-231346]
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DNA methylation inhibitors have become the mainstay for treatment of certain haematological malignancies. In addition to their abilities to reactivate genes, including tumour suppressors, that have acquired DNA methylation during carcinogenesis, they induce the expression of thousands of transposable elements including endogenous retroviruses and latent cancer testis antigens normally silenced by DNA methylation in most somatic cells. This results in a state of viral mimicry in which treated cells mount an innate immune response by turning on viral defence genes and potentially expressing neoantigens. Furthermore, these changes mediated by DNA methylation inhibitors can also alter the function of immune cells relevant to acquired immunity. Additionally, other inhibitors of epigenetic processes, such as histone deacetylases, methylases and demethylases, can elicit similar effects either individually or in combinations with DNA methylation inhibitors. These findings together with rapid development of immunotherapies open new avenues for cancer treatment.
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