Transposable Element Exprssion in Tumors is Associated with Immune Infiltration and Increased Antigenicity

Yu Kong, Chris Rose, Ashley A. Cass, Martine Darwish, Steve Lianoglou, Pete M. Haverty, Ann Jay Tong, Craig Blanchette, Ira Mellman, Richard Bourgon, John Greally, Suchit Jhunjhunwala, Matthew L. Albert, Haiyin Chen-Harris

Research output: Contribution to journalArticlepeer-review

Abstract

Profound loss of DNA methylation is a well-recognized hallmark of cancer. Given its role in silencing transposable elements (TEs), we hypothesized that extensive TE expression occurs in tumors with highly demethylated DNA. We developed REdiscoverTE, a computational method for quantifying genome-wide TE expression in RNA sequencing data. Using The Cancer Genome Atlas database, we observed increased expression of over 400 TE subfamilies, of which 262 appeared to result from a proximal loss of DNA methylation. The most recurrent TEs were among the evolutionarily youngest in the genome, predominantly expressed from intergenic loci, and associated with antiviral or DNA damage responses. Treatment of glioblastoma cells with a demethylation agent resulted in both increased TE expression and de novo presentation of TE-derived peptides on MHC class I molecules. Therapeutic reactivation of tumor-specific TEs may synergize with immunotherapy by inducing both inflammation and the display of potentially immunogenic neoantigens. One Sentence Summary Transposable element expression in tumors is associated with increased immune response and provides tumor-associated antigens

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Aug 9 2018

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Fingerprint Dive into the research topics of 'Transposable Element Exprssion in Tumors is Associated with Immune Infiltration and Increased Antigenicity'. Together they form a unique fingerprint.

Cite this