Pan-cancer analysis identifies tumor-specific antigens derived from transposable elements

Nat Genet. 2023 Apr;55(4):631-639. doi: 10.1038/s41588-023-01349-3. Epub 2023 Mar 27.


Cryptic promoters within transposable elements (TEs) can be transcriptionally reactivated in tumors to create new TE-chimeric transcripts, which can produce immunogenic antigens. We performed a comprehensive screen for these TE exaptation events in 33 TCGA tumor types, 30 GTEx adult tissues and 675 cancer cell lines, and identified 1,068 TE-exapted candidates with the potential to generate shared tumor-specific TE-chimeric antigens (TS-TEAs). Whole-lysate and HLA-pulldown mass spectrometry data confirmed that TS-TEAs are presented on the surface of cancer cells. In addition, we highlight tumor-specific membrane proteins transcribed from TE promoters that constitute aberrant epitopes on the extracellular surface of cancer cells. Altogether, we showcase the high pan-cancer prevalence of TS-TEAs and atypical membrane proteins that could potentially be therapeutically exploited and targeted.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antigens, Neoplasm / genetics
  • Cell Line
  • DNA Transposable Elements* / genetics
  • Humans
  • Neoplasms* / genetics
  • Promoter Regions, Genetic / genetics


  • DNA Transposable Elements
  • Antigens, Neoplasm