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Pan-cancer analysis identifies tumor-specific antigens derived from transposable elements
Open accessAbstract
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.
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“Intriguingly, a prior study uncovered the presence of tumor-specific antigens originating from certain repetitive sequences in various cancers, potentially eliciting immune responses25.”
From Multi-omics analysis identifies glioblastoma dependency on H3K9me3 methyltransferase activity (2025) · cites this paper as [25]
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Calendo, G., Chaunzwa, M., Dehzangi, I., Madžo, J., & Issa, J. J. (2026) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2615533123
Metadata
- Authors
- Shah, N. M., Jang, H. J., Liang, Y., Maeng, J. H., Tzeng, S.-C., Wu, A., Basri, N. L., Qu, X., Fan, C., Li, A., Katz, B., Li, D., Xing, X., Evans, B. S., & Wang, T.
- Affiliations
- Washington University in St. Louis (US)
- Van Andel Institute (US)
- Donald Danforth Plant Science Center (US)
- Corresponding author
- Wang, Ting
- ORCID
- Venue
- Nature Genetics
- Published
- 2023-03-27
- Volume
- 55
- Issue
- 4
- Pages
- 631-639
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC13152471
- OpenAlex
- W4360999762
- Cited by
- 175
- References
- 70
- Citations by year
- 2026: 40 · 2025: 61 · 2024: 46 · 2023: 27
- FWCI
- 22.95
- Type
- journal article
- Language
- en
- Open access
- green
- pmc.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- Funders
- National Human Genome Research Institute (R01HG007175, U01HG009391)
- National Institute of General Medical Sciences (T32GM007067)
- National Institute of Environmental Health Sciences (U24ES026699)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- transposable elements, cryptic promoter, tumor-specific antigens, cancer immunotherapy, membrane proteins, pan-cancer analysis, cancer cell lines
- MeSH terms
- Adult, Antigens, Neoplasm, Cell Line, DNA Transposable Elements, Humans, Neoplasms, Promoter Regions, Genetic
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