Macrophages/Microglia in the Glioblastoma Tumor Microenvironment

Ma, Jun; Chen, Clark C.; Li, Ming

doi:10.3390/ijms22115775

Cited by 39 publications

(31 citation statements)

References 119 publications

(129 reference statements)

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“… 32 Moreover, the total number of microglia cells does not vary with the grade of malignancy, but macrophages enrich in high-grade gliomas. 33 Our previous study also confirmed that macrophage, but not microglia, was identified with prognostic significance in glioma progression. 3 These results strengthened the important role of macrophages in glioma progression.…”

Section: Discussionsupporting

confidence: 76%

Dual role of ARPC1B in regulating the network between tumor-associated macrophages and tumor cells in glioblastoma

et al. 2022

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The tumor microenvironment (TME) plays a critical role in promoting the growth and metastasis of glioblastoma (GBM). Tumor-associated macrophages (TAMs), the most abundant myeloid cells infiltrating in TME, produce proinflammatory cytokines, regulate glioma cell pools, and lead to GBM progression. Understanding the mechanism of GBM-TAMs regulation can help to find new targeted therapeutic strategies against GBM. Based on the CGGA and TCGA GBM cohorts, ARPC1B was defined as the key macrophage-associated gene with prognostic value. Higher ARPC1B expression was associated with progressive malignancy, poor outcomes and TAM infiltration. We demonstrated that macrophage-expressed ARPC1B promoted the migration, invasion, and epithelial–mesenchymal transition of glioma cells. Glioma-intrinsic ARPC1B also maintained the malignant phenotype and promoted macrophage recruitment. Positive feedback signaling between macrophages and glioma cells via ARPC1B was determined to be under control of the IFNγ-IRF2-ARPC1B axis. This study highlights the important role of ARPC1B in GBM malignancy progression and the regulation network between GBM and TAMs, suggesting ARPC1B as a novel biomarker with potential therapeutic implications.

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Section: Discussionsupporting

confidence: 76%

Dual role of ARPC1B in regulating the network between tumor-associated macrophages and tumor cells in glioblastoma

et al. 2022

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“…Clinical studies have shown that there is a large number of microglia in GBM tissue [ 54 , 55 ]. GBM tissue promotes the polarization of microglia toward anti-inflammatory M2 type [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

Biomimetic GBM-targeted drug delivery system boosting ferroptosis for immunotherapy of orthotopic drug-resistant GBM

Liu

Cheng

et al. 2022

J Nanobiotechnol

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Background Clinical studies have shown that the efficacy of programmed cell death receptor-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitors on glioblastoma (GBM) is much lower than what is expected because of the low immunogenicity of GBM. Ferroptosis of cancer cells can induce the maturation of dendritic cells (DC cells) and increase the activity of T cell. The activated T cells release IFN-γ, which subsequently induces the ferroptosis of cancer cells. Thus, the aim of this paper is to set up a new GBM-targeted drug delivery system (Fe3O4-siPD-L1@M-BV2) to boost ferroptosis for immunotherapy of drug-resistant GBM. Results Fe3O4-siPD-L1@M-BV2 significantly increased the accumulation of siPD-L1 and Fe2+ in orthotopic drug-resistant GBM tissue in mice. Fe3O4-siPD-L1@M-BV2 markedly decreased the protein expression of PD-L1 and increased the ratio between effector T cells and regulatory T cells in orthotopic drug-resistant GBM tissue. Moreover, Fe3O4-siPD-L1@M-BV2 induced ferroptosis of GBM cells and maturation of DC cell, and it also increased the ratio between M1-type microglia and M2-type microglia in orthotopic drug-resistant GBM tissue. Finally, the growth of orthotopic drug-resistant GBM in mice was significantly inhibited by Fe3O4-siPD-L1@M-BV2. Conclusion The mutual cascade amplification effect between ferroptosis and immune reactivation induced by Fe3O4-siPD-L1@M-BV2 significantly inhibited the growth of orthotopic drug-resistant GBM and prolonged the survival time of orthotopic drug-resistant GBM mice. Graphical Abstract

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“…GAMs represent an important component of the glioma microenvironment ( 54 ) constituting the main proportion of infiltrating cells in adult and pediatric HGGs (i.e., glioblastoma and DIPG) ( 55 , 56 ). Inside the tumor, GAMs usually acquire a specific phenotype of activation that favors tumor growth, angiogenesis and promotes the invasion of normal brain parenchyma.…”

Section: Tumor Microenvironment In Adult and Pediatric High-grade Gliomamentioning

confidence: 99%

CAR-T Therapy for Pediatric High-Grade Gliomas: Peculiarities, Current Investigations and Future Strategies

et al. 2022

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High-Grade Gliomas (HGG) are among the deadliest malignant tumors of central nervous system (CNS) in pediatrics. Despite aggressive multimodal treatment - including surgical resection, radiotherapy and chemotherapy - long-term prognosis of patients remains dismal with a 5-year survival rate less than 20%. Increased understanding of genetic and epigenetic features of pediatric HGGs (pHGGs) revealed important differences with adult gliomas, which need to be considered in order to identify innovative and more effective therapeutic approaches. Immunotherapy is based on different techniques aimed to redirect the patient own immune system to fight specifically cancer cells. In particular, T-lymphocytes can be genetically modified to express chimeric proteins, known as chimeric antigen receptors (CARs), targeting selected tumor-associated antigens (TAA). Disialoganglioside GD2 (GD-2) and B7-H3 are highly expressed on pHGGs and have been evaluated as possible targets in pediatric clinical trials, in addition to the antigens common to adult glioblastoma – such as interleukin-13 receptor alpha 2 (IL-13α2), human epidermal growth factor receptor 2 (HER-2) and erythropoietin-producing human hepatocellular carcinoma A2 receptor (EphA2). CAR-T therapy has shown promise in preclinical model of pHGGs but failed to achieve the same success obtained for hematological malignancies. Several limitations, including the immunosuppressive tumor microenvironment (TME), the heterogeneity in target antigen expression and the difficulty of accessing the tumor site, impair the efficacy of T-cells. pHGGs display an immunologically cold TME with poor T-cell infiltration and scarce immune surveillance. The secretion of immunosuppressive cytokines (TGF-β, IL-10) and the presence of immune-suppressive cells – like tumor-associated macrophages/microglia (TAMs) and myeloid-derived suppressor cells (MDSCs) - limit the effectiveness of immune system to eradicate tumor cells. Innovative immunotherapeutic strategies are necessary to overcome these hurdles and improve ability of T-cells to eradicate tumor. In this review we describe the distinguishing features of HGGs of the pediatric population and of their TME, with a focus on the most promising CAR-T therapies overcoming these hurdles.

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Macrophages/Microglia in the Glioblastoma Tumor Microenvironment

Cited by 39 publications

References 119 publications

Dual role of ARPC1B in regulating the network between tumor-associated macrophages and tumor cells in glioblastoma

Dual role of ARPC1B in regulating the network between tumor-associated macrophages and tumor cells in glioblastoma

Biomimetic GBM-targeted drug delivery system boosting ferroptosis for immunotherapy of orthotopic drug-resistant GBM

CAR-T Therapy for Pediatric High-Grade Gliomas: Peculiarities, Current Investigations and Future Strategies

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