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

Reiner Strick; Pamela L Strissel; Stephen B Baylin; Katherine B Chiappinelli

doi:10.1080/2162402X.2015.1122160

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.

Authors

Reiner Strick¹, Pamela L Strissel¹, Stephen B Baylin², Katherine B Chiappinelli²

Affiliations

¹ Department of Gynecology and Obstetrics, Laboratory for Molecular Medicine, Friedrich-Alexander University Erlangen-Nürnberg (FAU), University-Clinic Erlangen , Erlangen, Germany.
² Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins , Baltimore, MD, USA.

Abstract

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.