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Review
. 2022 Aug 20;14(16):4023.
doi: 10.3390/cancers14164023.

Next Steps for Immunotherapy in Glioblastoma

Toni Q Cao  1 , Derek A Wainwright  2   3   4   5   6 , Catalina Lee-Chang  2   3 , Jason Miska  2   3 , Adam M Sonabend  2   3 , Amy B Heimberger  2   3 , Rimas V Lukas  1   3
Affiliations
Review

Next Steps for Immunotherapy in Glioblastoma

Toni Q Cao et al. Cancers (Basel). .

Abstract

Outcomes for glioblastoma (GBM) patients undergoing standard of care treatment remain poor. Here we discuss the portfolio of previously investigated immunotherapies for glioblastoma, including vaccine therapy and checkpoint inhibitors, as well as novel emerging therapeutic approaches. In addition, we explore the factors that potentially influence response to immunotherapy, which should be considered in future research aimed at improving immunotherapy efficacy.

Keywords: glioblastoma; immune system; immunotherapy.

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Conflict of interest statement

A.M.S. reports authorship of patents filed by Northwestern University regarding immunotherapy for gliomas. Research support has kindly been provided by BMS, Agenus, and Carthera. Additionally, he has received philanthropic support from Agenus. A.B.H. serves on the advisory board of Caris Life Sciences, and WCG Oncology Advisory Board receives royalty and milestone payments from DNAtrix for the licensing of “Biomarkers and combination therapies using oncolytic virus and immunomodulation” (11,065,285) and is supported by research grants from Celularity, Codiak Biosciences, and AbbVie. Other support has been provided by Moleculin and Carthera, and she has received consulting fees in the last year from Novocure and Istari Oncology. She additionally has active patents for “miRNA for treating cancer and for use with adoptive immunotherapies” (9,675,633) and “Concurrent chemotherapy and immunotherapy (9,399,662) with a patent pending for “Low intensity ultrasound combination cancer therapies” (International application #PCT/US2022/019435 and US 63/158,642). RVL serves on the scientific advisory board for Merck. Additionally, he is on the speakers’ bureau for Novocure and Merck. He receives research support from BMS. T.Q.C., D.A.W., C.L.C., and J.M. have no conflicts of interest to disclose.

Figures

Figure 1
Figure 1
EGFRvIII signaling pathways.
Figure 2
Figure 2
PD-1 and PD-L1 expression. PD-1 (programmed death-1) and PD-L1 (programmed death ligand 1) are expressed in T cell and cancer cells, respectively. Examples of PD-1 blockers include nivolumab, pembrolizumab, and cemiplimab. Examples of PD-L1 blockers include atezolizumab, durvalumab, and avelumab.
Figure 3
Figure 3
IDO1 promotes the immunosuppressive tumor microenvironment through multiple mechanisms. ↑, ↑↑ = increased, ↓ = decreased.
Figure 4
Figure 4
STAT3 promotes the immunosuppressive tumor microenvironment through multiple mechanisms. ↑, ↑↑ = increased, ↓ = decreased.
Figure 5
Figure 5
MDSCs can be targeted through various mechanisms. MDSCs (myeloid-derived suppressor cells) promote an immunosuppressive tumor microenvironment. Two main methods of targeting MDSCs include (1) inhibiting MDSC recruitment, such as with CCR2 (C-C chemokine receptor 2) blockade, as well as DFMO (difluormethylornithine) administration, and (2) reprogramming MDSCs to become immunostimulatory, such as with CSF1R (colony-stimulating factor 1 receptor) inhibition and niacin administration.
See this image and copyright information in PMC

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