Unraveling the molecular pathways of DNA-methylation inhibitors: human endogenous retroviruses induce the innate immune response in tumors

Oncoimmunology. 2015 Dec 29;5(5):e1122160. doi: 10.1080/2162402X.2015.1122160. eCollection 2016 May.


Loss of DNA methylation can activate endogenous retroviral expression and dsRNA in cancer cells. This leads to induction of toll-like receptor signaling stimulating an antiviral interferon response. Recent findings provide a therapeutic rationale for combining DNA methylation inhibitors with blockage of immune checkpoint proteins to fight cancer.

Keywords: DNA methylation; IFN-signalling; TLR; dsRNA; endogeneous retrovirus (ERV); epigenetic therapy; immune checkpoints; innate immunity.