Transposable element expression in tumors is associated with immune infiltration and increased antigenicity
| العنوان: | Transposable element expression in tumors is associated with immune infiltration and increased antigenicity |
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| المؤلفون: | Craig Blanchette, Peter M. Haverty, Haiyin Chen-Harris, Steve Lianoglou, Martine Darwish, Richard Bourgon, Alexander G. Williams, Ira Mellman, Ann Jay Tong, Christopher M. Rose, Suchit Jhunjhunwala, John M. Greally, Ashley A. Cass, Matthew L. Albert, Yu Kong |
| المصدر: | Nature Communications Nature Communications, Vol 10, Iss 1, Pp 1-14 (2019) |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Transposable element, DNA damage, Science, Gene Expression, General Physics and Astronomy, Biology, Genome, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigen, Antigens, Neoplasm, Cell Line, Tumor, Neoplasms, MHC class I, Cancer genomics, Humans, lcsh:Science, Multidisciplinary, Sequence Analysis, RNA, Gene Expression Profiling, fungi, food and beverages, Computational Biology, General Chemistry, DNA Methylation, Gene expression profiling, 030104 developmental biology, 030220 oncology & carcinogenesis, DNA methylation, DNA Transposable Elements, Cancer research, biology.protein, lcsh:Q, Immunotherapy |
| الوصف: | 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. Treatment with demethylation agents can reactivate transposable elements. Here in glioblastoma, the authors also show that this is accompanied by de novo presentation of TE-derived peptides on MHC class I molecules. |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4a0bc023d86dc1bb6660d392155a5e68Test https://doi.org/10.1038/s41467-019-13035-2Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4a0bc023d86dc1bb6660d392155a5e68 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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