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. 2022 Jan 24;13:809761. doi: 10.3389/fimmu.2022.809761

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Copyright © 2022 Liu, Ren, Weng, Xu, Li and Han

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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DNA demethylation restores ERV expression to induce viral mimicry. DNA demethylating drugs reactivate ERV promoters by inhibiting their methylation, resulting in bidirectional transcription of ERVs to produce dsRNAs, which are exported to the cytoplasm and sensed by pattern recognition receptors, such as MDA5. MDA5 binding to dsRNA induces recruitment of TANK-binding kinase 1 (TBK1) and aggregation of mitochondrial antiviral signaling protein (MAVs), which activate interferon regulatory factor 7(IRF7) by phosphorylation. Then, activated IRF7 moves into the nucleus and induces transcription of interferon-responsive genes (IRG). Consequently, type I/III interferons are produced, transported, and secreted into the tumor microenvironment. Secreted type I/III interferons increase the expression of antigen processing and antigen presentation mechanisms, improving the ability of cancer cells to present antigens.