Multi-omics analysis of glioblastoma cells’ sensitivity to oncolytic viruses

Anastasiya V. Lipatova, Alesya V. Soboleva, Vladimir A. Gorshkov, Julia A. Bubis, Elizaveta M. Solovyeva, George S. Krasnov, Dmitry V. Kochetkov, Pavel O. Vorobyev, Irina Y. Ilina, Sergei A. Moshkovskii, Frank Kjeldsen, Mikhail V. Gorshkov, Peter M. Chumakov*, Irina A. Tarasova*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Oncolytic viruses have gained momentum in the last decades as a promising tool for cancer treatment. Despite the progress, only a fraction of patients show a positive response to viral therapy. One of the key variable factors contributing to therapy outcomes is interferon-dependent antiviral mechanisms in tumor cells. Here, we evaluated this factor using patient-derived glioblas-toma multiforme (GBM) cultures. Cell response to the type I interferons’ (IFNs) stimulation was characterized at mRNA and protein levels. Omics analysis revealed that GBM cells overexpress in-terferon-stimulated genes (ISGs) and upregulate their proteins, similar to the normal cells. A con-served molecular pattern unambiguously differentiates between the preserved and defective re-sponses. Comparing ISGs’ portraits with titration-based measurements of cell sensitivity to a panel of viruses, the “strength” of IFN-induced resistance acquired by GBM cells was ranked. The study demonstrates that suppressing a single ISG and encoding an essential antiviral protein, does not necessarily increase sensitivity to viruses. Conversely, silencing IFIT3 and PLSCR1 genes in tumor cells can negatively affect the internalization of vesicular stomatitis and Newcastle disease viruses. We present evidence of a complex relationship between the interferon response genes and other factors affecting the sensitivity of tumor cells to viruses.

Original languageEnglish
Article number5268
JournalCancers
Volume13
Issue number21
Number of pages19
ISSN2072-6694
DOIs
Publication statusPublished - 1. Nov 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Antiviral mechanisms
  • Glioblastoma
  • Interferon
  • Multi-omic approaches
  • Oncolytic viruses
  • Pathway identification

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