Immune response in glioma’s microenvironment

Chen, Houminji; Li, Ming; Guo, Yanwu; Zhong, Yongsheng; He, Zhuoyi; Xu, Yuting; Zou, Junjie

doi:10.1515/iss-2019-0001

Cited by 25 publications

(32 citation statements)

References 124 publications

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“…This might contribute to the higher ability of these cells to invade the brain parenchyma persistently. Additionally, it has been shown that immune cells, including macrophages and microglia, also promote glioma invasion [48][49][50] . Considering that our experiments were performed in immunodeficient NOD-SCID mice, it remains to be elucidated whether interactions with immune cells potentially affect the invasive behaviour of glioma cells with different GFAPδ/α ratios.…”

Section: Discussionmentioning

confidence: 99%

GFAP splice variants fine-tune glioma cell invasion and tumour dynamics by modulating migration persistence

Uceda-Castro

Asperen

Vennin

et al. 2022

Sci Rep

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Glioma is the most common form of malignant primary brain tumours in adults. Their highly invasive nature makes the disease incurable to date, emphasizing the importance of better understanding the mechanisms driving glioma invasion. Glial fibrillary acidic protein (GFAP) is an intermediate filament protein that is characteristic for astrocyte- and neural stem cell-derived gliomas. Glioma malignancy is associated with changes in GFAP alternative splicing, as the canonical isoform GFAPα is downregulated in higher-grade tumours, leading to increased dominance of the GFAPδ isoform in the network. In this study, we used intravital imaging and an ex vivo brain slice invasion model. We show that the GFAPδ and GFAPα isoforms differentially regulate the tumour dynamics of glioma cells. Depletion of either isoform increases the migratory capacity of glioma cells. Remarkably, GFAPδ-depleted cells migrate randomly through the brain tissue, whereas GFAPα-depleted cells show a directionally persistent invasion into the brain parenchyma. This study shows that distinct compositions of the GFAPnetwork lead to specific migratory dynamics and behaviours of gliomas.

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Section: Discussionmentioning

confidence: 99%

GFAP splice variants fine-tune glioma cell invasion and tumour dynamics by modulating migration persistence

Uceda-Castro

Asperen

Vennin

et al. 2022

Sci Rep

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“…The tumour microenvironment is considered to play a key role in tumour cell invasion. Mounting evidence indicates that inflammatory factors are found in the tumour microenvironment of many cancers 4 . Pro‐inflammatory factors have been described in glioma, and it is generally considered that IL‐6, IL‐8, CXCL1, CXCL10 and TGFβ2 are pro‐tumour cytokines closely related to glioma progression 5‐9 .…”

Section: Introductionmentioning

confidence: 99%

“…factors are found in the tumour microenvironment of many cancers. 4 Pro-inflammatory factors have been described in glioma, and it is generally considered that IL-6, IL-8, CXCL1, CXCL10 and TGFβ2 are protumour cytokines closely related to glioma progression. [5][6][7][8][9] Interleukin-6 (IL-6) is a cytokine that regulates immune and inflammatory reactions.…”

mentioning

confidence: 99%

Csnk1a1 inhibition modulates the inflammatory secretome and enhances response to radiotherapy in glioma

Liu

Zhang

et al. 2021

J Cellular Molecular Medi

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Glioblastoma multiforme (GBM), a fatal brain tumour with no available targeted therapies, has a poor prognosis. At present, radiotherapy is one of the main methods to treat glioma, but it leads to an obvious increase in inflammatory factors in the tumour microenvironment, especially IL‐6 and CXCL1, which plays a role in tumour to resistance radiotherapy and tumorigenesis. Casein kinase 1 alpha 1 (CK1α) (encoded on chromosome 5q by Csnk1a1) is considered an attractive target for Tp53 wild‐type acute myeloid leukaemia (AML) treatment. In this study, we evaluated the anti‐tumour effect of Csnk1a1 suppression in GBM cells in vitro and in vivo. We found that down‐regulation of Csnk1a1 or inhibition by D4476, a Csnk1a1 inhibitor, reduced GBM cell proliferation efficiently in both Tp53 wild‐type and Tp53‐mutant GBM cells. On the contrary, overexpression of Csnk1a1 promoted cell proliferation and colony formation. Csnk1a1 inhibition improved the sensitivity to radiotherapy. Furthermore, down‐regulation of Csnk1a1 reduced the production and secretion of pro‐inflammatory factors. In the preclinical GBM model, treatment with D4476 significantly inhibited the increase in pro‐inflammatory factors caused by radiotherapy and improved radiotherapy sensitivity, thus inhibiting tumour growth and prolonging animal survival time. These results suggest targeting Csnk1a1 exert an anti‐tumour role as an inhibitor of inflammatory factors, providing a new strategy for the treatment of glioma.

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“…The profile of residual and non-residual cells in glioma seems to be associated with distinct molecular properties. For glioma, it is reported that M2 (anti-inflammatory macrophage phenotype) is activated via pro-cancerogenic IL-10 and TGF-beta (transforming growth factor) [ 111 ]. Exosomes from glioma cells of the hypoxic niche glioma foster M2 polarization [ 112 ].…”

Section: The Tme Immune-state Is Receptive To the Molecular Heterogen...mentioning

confidence: 99%

Glioma: molecular signature and crossroads with tumor microenvironment

Barthel¹,

Hadamitzky²,

Dammann³

et al. 2021

Cancer Metastasis Rev

107

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In patients with glioblastoma, the average survival time with current treatments is short, mainly due to recurrences and resistance to therapy. This insufficient treatment success is, in large parts, due to the tremendous molecular heterogeneity of gliomas, which affects the overall prognosis and response to therapies and plays a vital role in gliomas’ grading. In addition, the tumor microenvironment is a major player for glioma development and resistance to therapy. Active communication between glioma cells and local or neighboring healthy cells and the immune environment promotes the cancerogenic processes and contributes to establishing glioma stem cells, which drives therapy resistance. Besides genetic alterations in the primary tumor, tumor-released factors, cytokines, proteins, extracellular vesicles, and environmental influences like hypoxia provide tumor cells the ability to evade host tumor surveillance machinery and promote disease progression. Moreover, there is increasing evidence that these players affect the molecular biological properties of gliomas and enable inter-cell communication that supports pro-cancerogenic cell properties. Identifying and characterizing these complex mechanisms are inevitably necessary to adapt therapeutic strategies and to develop novel measures. Here we provide an update about these junctions where constant traffic of biomolecules adds complexity in the management of glioblastoma. Graphical abstract

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Immune response in glioma’s microenvironment

Cited by 25 publications

References 124 publications

GFAP splice variants fine-tune glioma cell invasion and tumour dynamics by modulating migration persistence

GFAP splice variants fine-tune glioma cell invasion and tumour dynamics by modulating migration persistence

Csnk1a1 inhibition modulates the inflammatory secretome and enhances response to radiotherapy in glioma

Glioma: molecular signature and crossroads with tumor microenvironment

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