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Published on: March 28, 2021
Immunomodulation Mediated by Anti-angiogenic Therapy Improves CD8 T Cell Immunity Against Experimental Glioma
Courtney S Malo1,2, Roman H Khadka1,2, Katayoun Ayasoufi1
1Department of Immunology, Mayo Clinic, Rochester, MN, United States.
Abstract:
Glioblastoma (GBM) is a lethal cancer of the central nervous system with a median survival rate of 15 months with treatment. Thus, there is a critical need to develop novel therapies for GBM. Immunotherapy is emerging as a promising therapeutic strategy. However, current therapies for GBM, in particular anti-angiogenic therapies that block vascular endothelial growth factor (VEGF), may have undefined consequences on the efficacy of immunotherapy. While this treatment is primarily prescribed to reduce tumor vascularization, multiple immune cell types also express VEGF receptors, including the most potent antigen-presenting cell, the dendritic cell (DC). Therefore, we assessed the role of anti-VEGF therapy in modifying DC function. We found that VEGF blockade results in a more mature DC phenotype in the brain, as demonstrated by an increase in the expression of the co-stimulatory molecules B7-1, B7-2, and MHC II. Furthermore, we observed reduced levels of the exhaustion markers PD-1 and Tim-3 on brain-infiltrating CD8 T cells, indicating improved functionality. Thus, anti-angiogenic therapy has the potential to be used in conjunction with and enhance immunotherapy for GBM.
Insights
Anti-angiogenic therapy targeting vascular endothelial growth factor (VEGF) enhances dendritic cell (DC) maturation and T cell function in glioblastoma (GBM). This suggests combining anti-VEGF treatments with immunotherapy could improve GBM treatment efficacy.
Area of Science:
- Neuro-oncology
- Immunology
- Cancer Therapy
Background:
- Glioblastoma (GBM) is an aggressive brain cancer with poor prognosis.
- Current GBM treatments, including anti-angiogenic therapies, may impact immunotherapy effectiveness.
- Vascular Endothelial Growth Factor (VEGF) signaling affects both tumor vasculature and immune cells like dendritic cells (DCs).
Purpose of the Study:
- To investigate the effects of anti-VEGF therapy on dendritic cell (DC) function in the context of glioblastoma (GBM).
- To determine if anti-VEGF therapy modulates immune cell populations and their functional status within the brain tumor microenvironment.
Main Methods:
- Assessment of dendritic cell (DC) maturation markers (B7-1, B7-2, MHC II) following VEGF blockade.
- Analysis of T cell exhaustion markers (PD-1, Tim-3) on brain-infiltrating CD8 T cells.
- In vivo studies in a glioblastoma model to evaluate therapeutic effects.
Main Results:
- VEGF blockade led to increased maturation of dendritic cells (DCs) in the brain.
- Reduced expression of exhaustion markers (PD-1, Tim-3) was observed on CD8 T cells.
- These findings indicate enhanced immune cell functionality in response to anti-VEGF therapy.
Conclusions:
- Anti-angiogenic therapy targeting VEGF promotes a more favorable immune microenvironment for glioblastoma treatment.
- VEGF blockade enhances dendritic cell maturation and T cell function, suggesting a synergistic potential with immunotherapy.
- Combining anti-VEGF strategies with immunotherapy may represent a novel therapeutic approach for glioblastoma.
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