@article{cb6c4d3243364283bc8f58344513d9c6,
title = "Pan-cancer analysis identifies tumor-specific antigens derived from transposable elements",
abstract = "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.",
author = "Shah, {Nakul M.} and Jang, {H. Josh} and Yonghao Liang and Maeng, {Ju Heon} and Tzeng, {Shin Cheng} and Angela Wu and Basri, {Noah L.} and Xuan Qu and Changxu Fan and Amy Li and Benjamin Katz and Daofeng Li and Xiaoyun Xing and Evans, {Bradley S.} and Ting Wang",
note = "Funding Information: We would like to thank Z. Andrysik and J.M. Espinosa from the Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA, for the generous gift of TP53-KO HCT116 cell line. We would like to thank J. Hoisington-L{\'o}pez and M.L. Jaeger from The Edison Family Center for Genome Sciences & Systems Biology (CGSSB) for assistance with sequencing and B. Koebbe and E. Martin from CGSSB for data processing. T.W. is funded by NIH grants 5R01HG007175, U24ES026699 and U01HG009391 and the American Cancer Society Research Scholar grant number RSG- 14-049-01-DMC awarded. N.M.S. was a Howard Hughes Medical Institute (H.H.M.I.) Medical Research Fellow. H.J.J. was supported by a grant from NIGMS (T32 GM007067). The LC–MS/MS work from the Proteomics & Mass Spectrometry Facility at the Danforth Plant Science Center is supported by National Science Foundation grant DBI-1827534 for the acquisition of the Orbitrap Fusion Lumos LC–MS/MS. Funding Information: We would like to thank Z. Andrysik and J.M. Espinosa from the Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA, for the generous gift of TP53-KO HCT116 cell line. We would like to thank J. Hoisington-L{\'o}pez and M.L. Jaeger from The Edison Family Center for Genome Sciences & Systems Biology (CGSSB) for assistance with sequencing and B. Koebbe and E. Martin from CGSSB for data processing. T.W. is funded by NIH grants 5R01HG007175, U24ES026699 and U01HG009391 and the American Cancer Society Research Scholar grant number RSG- 14-049-01-DMC awarded. N.M.S. was a Howard Hughes Medical Institute (H.H.M.I.) Medical Research Fellow. H.J.J. was supported by a grant from NIGMS (T32 GM007067). The LC–MS/MS work from the Proteomics & Mass Spectrometry Facility at the Danforth Plant Science Center is supported by National Science Foundation grant DBI-1827534 for the acquisition of the Orbitrap Fusion Lumos LC–MS/MS. Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2023",
month = apr,
doi = "10.1038/s41588-023-01349-3",
language = "English",
volume = "55",
pages = "631--639",
journal = "Nature Genetics",
issn = "1061-4036",
number = "4",
}