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Review

Challenges and Opportunities for Immunotherapeutic Intervention against Myeloid Immunosuppression in Glioblastoma

1
Imvax, Inc., Philadelphia, PA 19602, USA
2
Gastroenterology, Hepatology & Endoscopy, Brigham & Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
3
Faculty of Medical & Human Sciences, University of Manchester, Manchester M13 9NT, UK
4
Neurological Surgery, Thomas Jefferson University Medical School, Philadelphia, PA 19602, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Julia Kzhyshkowska
J. Clin. Med. 2022, 11(4), 1069; https://doi.org/10.3390/jcm11041069
Received: 24 January 2022 / Revised: 5 February 2022 / Accepted: 10 February 2022 / Published: 18 February 2022
Glioblastoma multiforme (GBM), the most common and deadly brain cancer, exemplifies the paradigm that cancers grow with help from an immunosuppressive tumor microenvironment (TME). In general, TME includes a large contribution from various myeloid lineage-derived cell types, including (in the brain) altered pathogenic microglia as well as monocyte-macrophages (Macs), myeloid-derived suppressor cells (MDSC) and dendritic cell (DC) populations. Each can have protective roles, but has, by definition, been coopted by the tumor in patients with progressive disease. However, evidence demonstrates that myeloid immunosuppressive activities can be reversed in different ways, leading to enthusiasm for this therapeutic approach, both alone and in combination with potentially synergistic immunotherapeutic and other strategies. Here, we review the current understanding of myeloid cell immunosuppression of anti-tumor responses as well as potential targets, challenges, and developing means to reverse immunosuppression with various therapeutics and their status. Targets include myeloid cell colony stimulating factors (CSFs), insulin-like growth factor 1 (IGF1), several cytokines and chemokines, as well as CD40 activation and COX2 inhibition. Approaches in clinical development include antibodies, antisense RNA-based drugs, cell-based combinations, polarizing cytokines, and utilizing Macs as a platform for Chimeric Antigen Receptors (CAR)-based tumor targeting, like with CAR-T cells. To date, promising clinical results have been reported with several of these approaches. View Full-Text
Keywords: cancer; GBM; immunotherapy; macrophages; M1; M2; MDSC; myeloid; therapeutic vaccine; tumor microenvironment (TME) cancer; GBM; immunotherapy; macrophages; M1; M2; MDSC; myeloid; therapeutic vaccine; tumor microenvironment (TME)
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MDPI and ACS Style

Exley, M.A.; Garcia, S.; Zellander, A.; Zilberberg, J.; Andrews, D.W. Challenges and Opportunities for Immunotherapeutic Intervention against Myeloid Immunosuppression in Glioblastoma. J. Clin. Med. 2022, 11, 1069. https://doi.org/10.3390/jcm11041069

AMA Style

Exley MA, Garcia S, Zellander A, Zilberberg J, Andrews DW. Challenges and Opportunities for Immunotherapeutic Intervention against Myeloid Immunosuppression in Glioblastoma. Journal of Clinical Medicine. 2022; 11(4):1069. https://doi.org/10.3390/jcm11041069

Chicago/Turabian Style

Exley, Mark A., Samantha Garcia, Amelia Zellander, Jenny Zilberberg, and David W. Andrews. 2022. "Challenges and Opportunities for Immunotherapeutic Intervention against Myeloid Immunosuppression in Glioblastoma" Journal of Clinical Medicine 11, no. 4: 1069. https://doi.org/10.3390/jcm11041069

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