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 and Haiyin Chen-Harris ()
Additional contact information
Yu Kong: Albert Einstein College of Medicine
Christopher M. Rose: Genentech, Inc., 1 DNA Way
Ashley A. Cass: University of California at Los Angeles
Alexander G. Williams: Genentech, Inc., 1 DNA Way
Martine Darwish: Genentech, Inc., 1 DNA Way
Steve Lianoglou: Genentech, Inc., 1 DNA Way
Peter M. Haverty: Genentech, Inc., 1 DNA Way
Ann-Jay Tong: Genentech, Inc., 1 DNA Way
Craig Blanchette: Genentech, Inc., 1 DNA Way
Matthew L. Albert: Genentech, Inc., 1 DNA Way
Ira Mellman: Genentech, Inc., 1 DNA Way
Richard Bourgon: Genentech, Inc., 1 DNA Way
John Greally: Albert Einstein College of Medicine
Suchit Jhunjhunwala: Genentech, Inc., 1 DNA Way
Haiyin Chen-Harris: Genentech, Inc., 1 DNA Way

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-13035-2

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