Radiation-Induced Cellular Senescence Reduces Susceptibility of Glioblastoma Cells to Oncolytic Vaccinia Virus

Glioblastoma (GBM) is a malignant brain cancer refractory to the current standard of care, prompting an extensive search for novel strategies to improve outcomes. One approach under investigation is oncolytic virus (OV) therapy in combination with radiotherapy. In addition to the direct cytocidal ef...

Full description

Saved in:

Bibliographic Details
Published in:	Cancers Vol. 15; no. 13; p. 3341
Main Authors:	Storozynsky, Quinn T, Han, Xuefei, Komant, Shae, Agopsowicz, Kate C, Potts, Kyle G, Gamper, Armin M, Godbout, Roseline, Evans, David H, Hitt, Mary M
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 25-06-2023 MDPI
Subjects:	Antiviral activity Antiviral agents Biotechnology industry Brain cancer Brain tumors Cancer therapies Cell proliferation Cells Cytotoxicity Fibroblasts Glioblastoma Glioblastoma cells Glioblastoma multiforme Growth factors Health aspects Infectivity Investigations Kinases Oncolysis Penicillin Phenotypes Proteins Radiation Radiation therapy Senescence Sodium Thermal cycling Vaccinia Viruses Alberta Canada United States United States > US senescence glioblastoma vaccinia virus oncolytic viruses radiation
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Glioblastoma (GBM) is a malignant brain cancer refractory to the current standard of care, prompting an extensive search for novel strategies to improve outcomes. One approach under investigation is oncolytic virus (OV) therapy in combination with radiotherapy. In addition to the direct cytocidal effects of radiotherapy, radiation induces cellular senescence in GBM cells. Senescent cells cease proliferation but remain viable and are implicated in promoting tumor progression. The interaction of viruses with senescent cells is nuanced; some viruses exploit the senescent state to their benefit, while others are hampered, indicating senescence-associated antiviral activity. It is unknown how radiation-induced cellular senescence may impact the oncolytic properties of OVs based on the vaccinia virus (VACV) that are used in combination with radiotherapy. To better understand this, we induced cellular senescence by treating GBM cells with radiation, and then evaluated the growth kinetics, infectivity, and cytotoxicity of an oncolytic VACV, ∆ Δ , as well as wild-type VACV in irradiated senescence-enriched and non-irradiated human GBM cell lines. Our results show that both viruses display attenuated oncolytic activities in irradiated senescence-enriched GBM cell populations compared to non-irradiated controls. These findings indicate that radiation-induced cellular senescence is associated with antiviral activity and highlight important considerations for the combination of VACV-based oncolytic therapies with senescence-inducing agents such as radiotherapy.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Current address: Department of Neurosurgery, First Hospital of Jilin University, Changchun 130021, China.
ISSN:	2072-6694 2072-6694
DOI:	10.3390/cancers15133341