Epigenetic therapy in immune-oncology

Area of Science:

• Oncology
• Immunology
• Epigenetics

Background:

• DNA methylation inhibitors are key treatments for hematological malignancies.
• Carcinogenesis involves DNA methylation silencing tumor suppressor genes.
• Transposable elements and cancer-testis antigens are normally silenced by DNA methylation.

Purpose of the Study:

• To explore how DNA methylation inhibitors impact gene expression and immune responses.
• To investigate the role of epigenetic modifications in cancer treatment.
• To assess the potential of combining epigenetic inhibitors with immunotherapies.

Main Methods:

• Analysis of gene expression changes induced by DNA methylation inhibitors.
• Assessment of innate and acquired immune responses in treated cells.
• Evaluation of epigenetic inhibitors like histone deacetylase inhibitors.

Main Results:

• DNA methylation inhibitors reactivate silenced genes, including tumor suppressors.
• Expression of transposable elements, endogenous retroviruses, and cancer-testis antigens is induced.
• Viral mimicry and innate immune responses are triggered, alongside altered immune cell function.
• Other epigenetic inhibitors show similar effects, individually or in combination.

Conclusions:

• DNA methylation inhibitors induce viral mimicry and immune responses, offering novel therapeutic avenues.
• Epigenetic modifications play a crucial role in cancer development and treatment.
• The combination of epigenetic inhibitors and immunotherapies presents a promising strategy for cancer treatment.