Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses.

ABSTRACT: Mesenchymal tumor subpopulations secrete pro-tumorigenic cytokines and promote treatment resistance^1-4. This phenomenon has been implicated in chemorefractory small cell lung cancer and resistance to targeted therapies^5-8, but remains incompletely defined. Here, we identify a subclass of endogenous retroviruses (ERVs) that engages innate immune signaling in these cells. Stimulated 3 prime antisense retroviral coding sequences (SPARCS) are oriented inversely in 3' untranslated regions of specific genes enriched for regulation by STAT1 and EZH2. Derepression of these loci results in double-stranded RNA generation following IFN-γ exposure due to bi-directional transcription from the STAT1-activated gene promoter and the 5' long terminal repeat of the antisense ERV. Engag

SUBMITTER: Canadas I 

PROVIDER: S-EPMC6082722 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature