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Review

Tumor-Associated Macrophages/Microglia in Glioblastoma Oncolytic Virotherapy: A Double-Edged Sword

by
Sarah E. Blitz
1,
Ari D. Kappel
1,2,
Florian A. Gessler
3,
Neil V. Klinger
1,2,
Omar Arnaout
1,2,
Yi Lu
1,2,
Pier Paolo Peruzzi
1,2,
Timothy R. Smith
1,2,
Ennio A. Chiocca
1,2,
Gregory K. Friedman
4 and
Joshua D. Bernstock
1,2,*
1
Harvard Medical School, Boston, MA 02115, USA
2
Department of Neurosurgery, Brigham and Women’s Hospital, Boston, MA 02115, USA
3
Department of Neurosurgery, University Medicine Rostock, 18057 Rostock, Germany
4
Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35294, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2022, 23(3), 1808; https://doi.org/10.3390/ijms23031808
Submission received: 1 January 2022 / Revised: 29 January 2022 / Accepted: 1 February 2022 / Published: 4 February 2022
(This article belongs to the Special Issue Macrophages in the Glioblastoma Tumor Microenvironment)
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Abstract

Oncolytic virotherapy is a rapidly progressing field that uses oncolytic viruses (OVs) to selectively infect malignant cells and cause an antitumor response through direct oncolysis and stimulation of the immune system. Despite demonstrated pre-clinical efficacy of OVs in many cancer types and some favorable clinical results in glioblastoma (GBM) trials, durable increases in overall survival have remained elusive. Recent evidence has emerged that tumor-associated macrophage/microglia (TAM) involvement is likely an important factor contributing to OV treatment failure. It is prudent to note that the relationship between TAMs and OV therapy failures is complex. Canonically activated TAMs (i.e., M1) drive an antitumor response while also inhibiting OV replication and spread. Meanwhile, M2 activated TAMs facilitate an immunosuppressive microenvironment thereby indirectly promoting tumor growth. In this focused review, we discuss the complicated interplay between TAMs and OV therapies in GBM. We review past studies that aimed to maximize effectiveness through immune system modulation—both immunostimulatory and immunosuppressant—and suggest future directions to maximize OV efficacy.
Keywords: tumor-associated macrophages/microglia (TAMs); oncolytic virotherapy; tumor microenvironment; glioblastoma (GBM) tumor-associated macrophages/microglia (TAMs); oncolytic virotherapy; tumor microenvironment; glioblastoma (GBM)

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MDPI and ACS Style

Blitz, S.E.; Kappel, A.D.; Gessler, F.A.; Klinger, N.V.; Arnaout, O.; Lu, Y.; Peruzzi, P.P.; Smith, T.R.; Chiocca, E.A.; Friedman, G.K.; et al. Tumor-Associated Macrophages/Microglia in Glioblastoma Oncolytic Virotherapy: A Double-Edged Sword. Int. J. Mol. Sci. 2022, 23, 1808. https://doi.org/10.3390/ijms23031808

AMA Style

Blitz SE, Kappel AD, Gessler FA, Klinger NV, Arnaout O, Lu Y, Peruzzi PP, Smith TR, Chiocca EA, Friedman GK, et al. Tumor-Associated Macrophages/Microglia in Glioblastoma Oncolytic Virotherapy: A Double-Edged Sword. International Journal of Molecular Sciences. 2022; 23(3):1808. https://doi.org/10.3390/ijms23031808

Chicago/Turabian Style

Blitz, Sarah E., Ari D. Kappel, Florian A. Gessler, Neil V. Klinger, Omar Arnaout, Yi Lu, Pier Paolo Peruzzi, Timothy R. Smith, Ennio A. Chiocca, Gregory K. Friedman, and et al. 2022. "Tumor-Associated Macrophages/Microglia in Glioblastoma Oncolytic Virotherapy: A Double-Edged Sword" International Journal of Molecular Sciences 23, no. 3: 1808. https://doi.org/10.3390/ijms23031808

APA Style

Blitz, S. E., Kappel, A. D., Gessler, F. A., Klinger, N. V., Arnaout, O., Lu, Y., Peruzzi, P. P., Smith, T. R., Chiocca, E. A., Friedman, G. K., & Bernstock, J. D. (2022). Tumor-Associated Macrophages/Microglia in Glioblastoma Oncolytic Virotherapy: A Double-Edged Sword. International Journal of Molecular Sciences, 23(3), 1808. https://doi.org/10.3390/ijms23031808

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