Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/ijms23031808
Keywords
tumor-associated macrophages; microglia (TAMs); oncolytic virotherapy; tumor microenvironment; glioblastoma (GBM)
Funding
- Food and Drug Administration [R01FD006368, R01FD005379]
- Cannonball Kids cancer Foundation
- Hyundai Hope on Wheels
- Rally Foundation for Childhood Cancer Research
- CureSearch for Children's Cancer
- The V Foundation
- Andrew McDonough B+ Foundation
- National Pediatric Cancer Foundation
- Pediatric Cancer Research Foundation
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Oncolytic virotherapy uses viruses to selectively infect malignant cells and stimulate antitumor response. The involvement of tumor-associated macrophage/microglia appears to play a crucial role in the failure of oncolytic virotherapy.
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.
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