The role of human endogenous retroviruses in gliomas: From etiological perspectives and therapeutic implications

Ashish H. Shah, Mark Gilbert, Michael E. Ivan, Ricardo J. Komotar, John Heiss, Avindra Nath

Research output: Contribution to journalArticlepeer-review

Abstract

Accounting for approximately 8% of the human genome, human endogenous retroviruses (HERVs) have been implicated in a variety of cancers including gliomas. In normal cells, tight epigenetic regulation of HERVs prevent aberrant expression; however, in cancer cells, HERVs expression remains pervasive, suggesting a role of HERVs in oncogenic transformation. HERVs may contribute to oncogenesis in several ways including insertional mutagenesis, chromosomal rearrangements, proto-oncogene formation, and maintenance of stemness. On the other hand, recent data has suggested that reversing epigenetic silencing of HERVs may induce robust anti-tumor immune responses, suggesting HERVs' potential therapeutic utility in gliomas. By reversing epigenetic modifications that silence HERVs, DNA methyltransferase, and histone deacetylase inhibitors may stimulate a viral-mimicry cascade via HERV-derived dsRNA formation that induces interferon-mediated apoptosis. Leveraging this anti-tumor autoimmune response may be a unique avenue to target certain subsets of epigenetically-dysregulated gliomas. Nevertheless, the role of HERVs in gliomas as either arbitrators of oncogenesis or forerunners of the innate anti-tumor immune response remains unclear. Here, we review the role of HERVs in gliomas, their potential dichotomous function in propagating oncogenesis and stimulating the anti-tumor immune response, and identify future directions for research.

Original languageEnglish (US)
Pages (from-to)1647-1655
Number of pages9
JournalNeuro-Oncology
Volume23
Issue number10
DOIs
StatePublished - Oct 1 2021

Keywords

  • etiology
  • glioma
  • human endogenous retrovirus
  • viral mimicry

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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