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

Author

Listed:
  • Yu Kong

    (Albert Einstein College of Medicine)

  • Christopher M. Rose

    (Genentech, Inc., 1 DNA Way)

  • Ashley A. Cass

    (University of California at Los Angeles)

  • Alexander G. Williams

    (Genentech, Inc., 1 DNA Way)

  • Martine Darwish

    (Genentech, Inc., 1 DNA Way)

  • Steve Lianoglou

    (Genentech, Inc., 1 DNA Way)

  • Peter M. Haverty

    (Genentech, Inc., 1 DNA Way)

  • Ann-Jay Tong

    (Genentech, Inc., 1 DNA Way)

  • Craig Blanchette

    (Genentech, Inc., 1 DNA Way)

  • Matthew L. Albert

    (Genentech, Inc., 1 DNA Way)

  • Ira Mellman

    (Genentech, Inc., 1 DNA Way)

  • Richard Bourgon

    (Genentech, Inc., 1 DNA Way)

  • John Greally

    (Albert Einstein College of Medicine)

  • Suchit Jhunjhunwala

    (Genentech, Inc., 1 DNA Way)

  • Haiyin Chen-Harris

    (Genentech, Inc., 1 DNA Way
    Argonaut Genomics, Inc.)

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.

Suggested Citation

  • 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 & Rich, 2019. "Transposable element expression in tumors is associated with immune infiltration and increased antigenicity," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13035-2
    DOI: 10.1038/s41467-019-13035-2
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    Cited by:

    1. Nathália de Sousa Pereira & Glauco Akelinghton Freire Vitiello & Bruna Karina Banin-Hirata & Glaura Scantamburlo Alves Fernandes & Maria José Sparça Salles & Marla Karine Amarante & Maria Angelica Eha, 2020. "Mouse Mammary Tumor Virus (MMTV)-Like env Sequence in Brazilian Breast Cancer Samples: Implications in Clinicopathological Parameters in Molecular Subtypes," IJERPH, MDPI, vol. 17(24), pages 1-14, December.
    2. Ashish Goyal & Jens Bauer & Joschka Hey & Dimitris N. Papageorgiou & Ekaterina Stepanova & Michael Daskalakis & Jonas Scheid & Marissa Dubbelaar & Boris Klimovich & Dominic Schwarz & Melanie Märklin &, 2023. "DNMT and HDAC inhibition induces immunogenic neoantigens from human endogenous retroviral element-derived transcripts," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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