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Cited by 285Epigenetics and DNA MethylationChromosomal and Genetic VariationsCancer Immunotherapy and Biomarkers

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

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Kong, Yu, Rose, Christopher M., Cass, Ashley A., Williams, Alexander G., Darwish, Martine, Lianoglou, Steve, Haverty, Peter M., Tong, Ann-Jay +7 more·2019·Nature Communications
DOI 10.1038/s41467-019-13035-2PMC PMC6864081

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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.

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Authors
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.
Affiliations
  • Albert Einstein College of Medicine (US)
  • Genentech (US)
  • University of California, Los Angeles (US)
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2019-11-19
Volume
10
Issue
1
Pages
5228-5228
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-019-13035-2
PMC
PMC6864081
OpenAlex
W2989996227
Cited by
285
References
9
Citations by year
2026: 36 · 2025: 57 · 2024: 50 · 2023: 45 · 2022: 32 · 2021: 43 · 2020: 17 · 2019: 4 · 2018: 1
FWCI
7.94
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords
transposable elements, transposable element expression, DNA methylation loss, tumor immune infiltration, neoantigens, MHC class I antigen presentation, glioblastoma, demethylation, antiviral response, DNA damage response, immunotherapy, tumor immunology
MeSH terms
Antigens, Neoplasm, DNA Transposable Elements, Humans, Immunotherapy, Neoplasms, Gene Expression, Sequence Analysis, RNA, DNA Methylation, Computational Biology, Gene Expression Profiling, Cell Line, Tumor

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