The role of human endogenous retroviruses in gliomas: from etiological perspectives and therapeutic implications. Issue 10 (12th June 2021)

• Record Type: Journal Article
• Authors: Shah, Ashish H; Gilbert, Mark; Ivan, Michael E; Komotar, Ricardo J; Heiss, John; Nath, Avindra
• Is Part Of: Neuro-oncology. Volume 23:Issue 10(2021)
• Page Start: 1647
• Page End: 1655
• Publication Date: 2021-06-12
• Subjects: etiology -- glioma -- human endogenous retrovirus -- viral mimicry; Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noab142
• Languages: English
• ISSNs: 1522-8517

Abstract

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.