Transposable element expression in tumors is associated with immune infiltration and increased antigenicity

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

Research output: Contribution to journalArticle

Abstract

Profound global loss of DNA methylation is a hallmark of many cancers. One potential consequence of this is the reactivation of transposable elements (TEs) which could stimulate the immune system via cell-intrinsic antiviral responses. Here, we develop REdiscoverTE, a computational method for quantifying genome-wide TE expression in RNA sequencing data. Using The Cancer Genome Atlas database, we observe increased expression of over 400 TE subfamilies, of which 262 appear to result from a proximal loss of DNA methylation. The most recurrent TEs are 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 results 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 inflammation and the display of potentially immunogenic neoantigens.

Original languageEnglish (US)
Article number5228
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Kong, Y., Rose, C. M., Cass, A. A., Williams, A. G., Darwish, M., Lianoglou, S., Haverty, P. M., Tong, A. J., Blanchette, C., Albert, M. L., Mellman, I., Bourgon, R., Greally, J., Jhunjhunwala, S., & Chen-Harris, H. (2019). Transposable element expression in tumors is associated with immune infiltration and increased antigenicity. Nature communications, 10(1), [5228]. https://doi.org/10.1038/s41467-019-13035-2