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

Yu Kong; Christopher M. Rose; Ashley A. Cass; Alexander G. Williams; Martine Darwish; Steve Lianoglou; Peter M. Haverty; Ann Jay Tong; Craig Blanchette; Matthew L. Albert; Ira Mellman; Richard Bourgon; John Greally; Suchit Jhunjhunwala; Haiyin Chen-Harris

doi:10.1038/s41467-019-13035-2

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

Yu Kong, Christopher M. Rose, Ashley A. Cass, Alexander G. Williams, Martine Darwish, Steve Lianoglou, Peter M. Haverty, Ann Jay Tong, Craig Blanchette, Matthew L. Albert, Ira Mellman, Richard Bourgon, John Greally, Suchit Jhunjhunwala, Haiyin Chen-Harris

Genetics

Research output: Contribution to journal › Article › peer-review

87 Scopus citations

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.

Original language	English (US)
Article number	5228
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-13035-2
State	Published - Dec 1 2019

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
General
Physics and Astronomy(all)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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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. (2019). Transposable element expression in tumors is associated with immune infiltration and increased antigenicity. Nature communications, 10(1), [5228]. https://doi.org/10.1038/s41467-019-13035-2

Kong, Y, Rose, CM, Cass, AA, Williams, AG, Darwish, M, Lianoglou, S, Haverty, PM, Tong, AJ, Blanchette, C, Albert, ML, Mellman, I, Bourgon, R, Greally, J, Jhunjhunwala, S & Chen-Harris, H 2019, 'Transposable element expression in tumors is associated with immune infiltration and increased antigenicity', Nature communications, vol. 10, no. 1, 5228. https://doi.org/10.1038/s41467-019-13035-2

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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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AU - Blanchette, Craig

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AU - Mellman, Ira

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

Abstract

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