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Review
. 2023 Oct 4:11:1271575.
doi: 10.3389/fcell.2023.1271575. eCollection 2023.

Positioning SUMO as an immunological facilitator of oncolytic viruses for high-grade glioma

Paramesh V Karandikar  1   2 , Lyle Suh  1 , Jakob V E Gerstl  2 , Sarah E Blitz  2 , Qing Rui Qu  2 , Sae-Yeon Won  3 , Florian A Gessler  3 , Omar Arnaout  2 , Timothy R Smith  2 , Pier Paolo Peruzzi  2 , Wei Yang  4 , Gregory K Friedman  5 , Joshua D Bernstock  2   6
Affiliations
Review

Positioning SUMO as an immunological facilitator of oncolytic viruses for high-grade glioma

Paramesh V Karandikar et al. Front Cell Dev Biol. .

Abstract

Oncolytic viral (OV) therapies are promising novel treatment modalities for cancers refractory to conventional treatment, such as glioblastoma, within the central nervous system (CNS). Although OVs have received regulatory approval for use in the CNS, efficacy is hampered by obstacles related to delivery, under-/over-active immune responses, and the "immune-cold" nature of most CNS malignancies. SUMO, the Small Ubiquitin-like Modifier, is a family of proteins that serve as a high-level regulator of a large variety of key physiologic processes including the host immune response. The SUMO pathway has also been implicated in the pathogenesis of both wild-type viruses and CNS malignancies. As such, the intersection of OV biology with the SUMO pathway makes SUMOtherapeutics particularly interesting as adjuvant therapies for the enhancement of OV efficacy alone and in concert with other immunotherapeutic agents. Accordingly, the authors herein provide: 1) an overview of the SUMO pathway and its role in CNS malignancies; 2) describe the current state of CNS-targeted OVs; and 3) describe the interplay between the SUMO pathway and the viral lifecycle and host immune response.

Keywords: SUMO; SUMOtherapeutics; cancer immunotherapies; high-grade glioma; oncolytic viruses.

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Conflict of interest statement

JB has an equity position in Treovir Inc., a clinical stage oHSV company and is a member of the board of scientific advisors for Upfront Diagnostics, Centile Biosciences, and NeuroX1. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

FIGURE 1
FIGURE 1
SUMOtherapeutics as a means to counter tumor adaptations.
FIGURE 2
FIGURE 2
SUMO and its impact on host immunity, viral physiology, and cancer.
FIGURE 3
FIGURE 3
SUMO and the type I interferon response.
See this image and copyright information in PMC

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References

    1. Adorisio S., Fierabracci A., Muscari I., Liberati A. M., Ayroldi E., Migliorati G., et al. (2017). SUMO proteins: guardians of immune system. J. Autoimmun. 84, 21–28. 10.1016/j.jaut.2017.09.001 - DOI - PubMed
    1. Allen C., Paraskevakou G., Liu C., Iankov I. D., Msaouel P., Zollman P., et al. (2008). Oncolytic measles virus strains in the treatment of gliomas. Expert Opin. Biol. Ther. 8 (2), 213–220. 10.1517/14712598.8.2.213 - DOI - PMC - PubMed
    1. Bagley S. J., Desai A. S., Linette G. P., June C. H., O'Rourke D. M. (2018). CAR T-cell therapy for glioblastoma: recent clinical advances and future challenges. Neuro Oncol. 20 (11), 1429–1438. 10.1093/neuonc/noy032 - DOI - PMC - PubMed
    1. Bellail A., Hao C. (2016). Abstract 4546: ubc9 sumoylation is required for its interaction with CDK6 through SUMO-interacting motif (SIM) and regulates CDK6 sumoylation in glioblastoma. Cancer Res. 76 (14), 4546. 10.1158/1538-7445.am2016-4546 - DOI - PubMed
    1. Bellail A. C., Jin H. R., Lo H. Y., Jung S. H., Hamdouchi C., Kim D., et al. (2021). Ubiquitination and degradation of SUMO1 by small-molecule degraders extends survival of mice with patient-derived tumors. Sci. Transl. Med. 13 (615), eabh1486. 10.1126/scitranslmed.abh1486 - DOI - PMC - PubMed