Multiple Faces of the Glioblastoma Microenvironment

Şovrea, Alina Simona; Boşca, Bianca Adina; Melincovici, Carmen Stanca; Constantin, Anne-Marie; Crintea, Andreea; Mărginean, Mariana; Dronca, Eleonora; Jianu, Mihaela Elena; Sufleţel, Rada Teodora; Gonciar, Diana; Bungardean, Maria; Crivii, Carmen

doi:10.3390/ijms23020595

Cited by 10 publications

(6 citation statements)

References 166 publications

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“…Similarly, Lange and colleagues (2021) have recently highlighted a link between glioblastoma and tumor-associated epilepsy describing the processes leading to the dysregulation of the glutamatergic signaling, including imbalance of the redox system [ 41 ]. In addition, the imbalance of the brain redox status due to the presence of GBM has been also associated with the presence of parenchymal and peritumoral edema [ 42 ]. However, the identification of the specific determinants responsible for such detrimental associations between GBM and neuronal structure has not been elucidated yet.…”

Section: Discussionmentioning

confidence: 99%

Potential Neurotoxic Effects of Glioblastoma-Derived Exosomes in Primary Cultures of Cerebellar Neurons via Oxidant Stress and Glutathione Depletion

et al. 2022

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High-grade gliomas are the most fatal brain tumors. Grade 4 gliomas are called glioblastoma multiforme (GBM), which are associated with the poorest survival and a 5-year survival rate of less than 4%. Many patients with GBM developed concomitant cognitive dysfunctions and epilepsy. Although the cognitive decline is well defined in glioblastomas, the neurotoxic factors underlying this pathology are not well understood in GBM patients. In this study, we aimed to investigate whether GBM-derived exosomes play a role in neuronal toxicity. For this purpose, exosomes obtained from T98G and U373 GBM cells were applied to primary neuron culture at different concentrations. Subsequently, MTT, LDH, GSH, TAS, and TOS tests were performed. Both GBM-derived exosomes induced a dose-dependent and statistically significant increase of LDH release in cerebellar neurons. MTT assay revealed as both T98G and U373 GBM-derived exosomes induced dose-dependent neurotoxic effects in cerebellar neurons. To the best of our knowledge, this study is the first study demonstrating the toxic potential of GBM-derived exosomes to primary neurons, which may explain the peritumoral edema and cognitive decline in GBM patients.

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Section: Discussionmentioning

confidence: 99%

Potential Neurotoxic Effects of Glioblastoma-Derived Exosomes in Primary Cultures of Cerebellar Neurons via Oxidant Stress and Glutathione Depletion

et al. 2022

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“…Preliminary transcriptomic analyses aimed at deriving a risk score grounded on INF-γ expression posited that elevated INF-γ levels correlated with a more adverse clinicopathological and molecular prognosis in glioblastoma ( 59 , 60 ). Simultaneously, TNF-α exhibited heightened expression in GBM and was implicated in bolstering tumor proliferation ( 61 ). Current literature remains scant regarding the roles of INF-α and the complement system in glioblastoma.…”

Section: Discussionmentioning

confidence: 99%

High expression of BTN3A1 is associated with clinical and immunological characteristics and predicts a poor prognosis in advanced human gliomas

Kone,

Ghouzlani,

Qandouci

et al. 2024

Front. Immunol.

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IntroductionGliomas represent the most prevalent and aggressive tumors within the central nervous system. Despite the current standard treatments, the median survival time for glioblastoma patients remains dismal, hovering around 14 months. While attempts have been made to inhibit the PD-1/PD-L1 and CTLA-4/CD80-CD86 axes through immunotherapy, the outcomes have yet to demonstrate significant efficacy. The immune checkpoint Butyrophilin 3A1 (BTN3A1) can either be involved in advantageous or detrimental function depending on the cancer type.MethodsIn our study, we utilized a Moroccan cohort to delve into the role of BTN3A1 in gliomas. A transcriptomic analysis was conducted on 34 patients, which was then corroborated through a protein analysis in 27 patients and validated using the TCGA database (n = 667).ResultsOur results revealed an elevated expression of BTN3A1 in glioblastoma (grade 4), as evidenced in both the TCGA database and our cohort of Moroccan glioma patients. Within the TCGA cohort, BTN3A1 expression was notably higher in patients with wild-type IDH. We observed a positive correlation between BTN3A1 expression and immune infiltration of B cells, CD8+ T cells, naive CD4+ T cells, and M2 macrophages. Patients exhibiting increased BTN3A1 expression also presented elevated levels of TGF‐β, IL‐10, and TIM‐3 compared to those with reduced BTN3A1 expression. Notably, patients with high BTN3A1 expression were associated with a poorer prognosis than their counterparts with lower expression.ConclussionOur findings suggest that BTN3A1 might promote the establishment of an immunosuppressive microenvironment. Consequently, targeting BTN3A1 could offer novel therapeutic avenues for the management of advanced gliomas.

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“…Therefore, we can sustain that GSCs are promoting themselves. The vasculogenic mimicry occurs mostly in aggressive glioma, primarily associated with hypoxic conditions, and can contribute to resistance to anti-angiogenic therapies [ 170 , 180 , 198 ].…”

Section: Glioma Stem Cellsmentioning

confidence: 99%

Glioblastoma Microenvironment and Cellular Interactions

Crivii

Boșca

Melincovici

et al. 2022

Cancers

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The central nervous system (CNS) represents a complex network of different cells, such as neurons, glial cells, and blood vessels. In tumor pathology, glial cells result in the highest number of cancers, and glioblastoma (GB) is considered the most lethal tumor in this region. The development of GB leads to the infiltration of healthy tissue through the interaction between all the elements of the brain network. This results in a GB microenvironment, a complex peritumoral hallo composed of tumor cells and several non-tumor cells (e.g., nervous cells, stem cells, fibroblasts, vascular and immune cells), which might be the principal factor for the ineffective treatment due to the fact that the microenvironment modulates the biologic status of the tumor with the increase in its evasion capacity. Crosstalk between glioma cells and the brain microenvironment finally inhibits the beneficial action of molecular pathways, favoring the development and invasion of the tumor and its increasing resistance to treatment. A deeper understanding of cell–cell interactions in the tumor microenvironment (TME) and with the tumor cells could be the basis for a more efficient therapy.

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Multiple Faces of the Glioblastoma Microenvironment

Cited by 10 publications

References 166 publications

Potential Neurotoxic Effects of Glioblastoma-Derived Exosomes in Primary Cultures of Cerebellar Neurons via Oxidant Stress and Glutathione Depletion

Potential Neurotoxic Effects of Glioblastoma-Derived Exosomes in Primary Cultures of Cerebellar Neurons via Oxidant Stress and Glutathione Depletion

High expression of BTN3A1 is associated with clinical and immunological characteristics and predicts a poor prognosis in advanced human gliomas

Glioblastoma Microenvironment and Cellular Interactions

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