Oncolytic virotherapy: The cancer cell side

Research output: Contribution to journalReview articlepeer-review

Abstract

Cell autonomous immunity genes mediate the multiple stages of anti-viral defenses, including recognition of invading pathogens, inhibition of viral replication, reprogramming of cellular metabolism, programmed-cell-death, paracrine induction of antiviral state, and activation of im-munostimulatory inflammation. In tumor development and/or immunotherapy settings, selective pressure applied by the immune system results in tumor immunoediting, a reduction in the im-munostimulatory potential of the cancer cell. This editing process comprises the reduced expression and/or function of cell autonomous immunity genes, allowing for immune-evasion of the tumor while concomitantly attenuating anti-viral defenses. Combined with the oncogene-enhanced ana-bolic nature of cancer-cell metabolism, this attenuation of antiviral defenses contributes to viral replication and to the selectivity of oncolytic viruses (OVs) towards malignant cells. Here, we review the manners by which oncogene-mediated transformation and tumor immunoediting combine to alter the intracellular milieu of tumor cells, for the benefit of OV replication. We also explore the functional connection between oncogenic signaling and epigenetic silencing, and the way by which restriction of such silencing results in immune activation. Together, the picture that emerges is one in which OVs and epigenetic modifiers are part of a growing therapeutic toolbox that employs activation of anti-tumor immunity for cancer therapy.

Original languageEnglish
Article number939
Pages (from-to)1-19
Number of pages19
JournalCancers
Volume13
Issue number5
DOIs
StatePublished - 1 Mar 2021

Funding

FundersFunder number
DKFZ-MOST0123955
Emerson Collective Cancer Research Fund
German Cancer Research Fund-Israel Ministry of Science and Technology
Rosetrees FoundationPGS19-2/10160
Israel Cancer Association20200132
Israel Science Foundation470/17, 1966/18

    Keywords

    • DNA Methyltransferase inhibitor (DNMTi)
    • Epigenetic silencing
    • Immunoediting
    • Oncogenic signaling
    • Oncolytic viruses
    • RAS
    • Viral mimicry

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