Cell‑based immunotherapy of glioblastoma multiforme (Review)

Bryukhovetskiy, Igor

doi:10.3892/ol.2022.13253

Cited by 8 publications

(5 citation statements)

References 153 publications

(148 reference statements)

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“…Despite molecular advancements, there is still a considerable need for glioblastoma biomarkers[ 231 ], especially since the relatively ineffective treatment leaves the patients with a very dismal chance of survival[ 232 ]. One of the glioblastoma traits involved in the absence of effective treatment is tumor heterogeneity which can be explained by clonal evolution and the presence of stem cells[ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Delineating the glioblastoma stemness by genes involved in cytoskeletal rearrangements and metabolic alterations

Kałuzińska¹,

Kołat²,

Kośla³

et al. 2023

World J Stem Cells

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Literature data on glioblastoma ongoingly underline the link between metabolism and cancer stemness, the latter is one responsible for potentiating the resistance to treatment, inter alia due to increased invasiveness. In recent years, glioblastoma stemness research has bashfully introduced a key aspect of cytoskeletal rearrangements, whereas the impact of the cytoskeleton on invasiveness is well known. Although non-stem glioblastoma cells are less invasive than glioblastoma stem cells (GSCs), these cells also acquire stemness with greater ease if characterized as invasive cells and not tumor core cells. This suggests that glioblastoma stemness should be further investigated for any phenomena related to the cytoskeleton and metabolism, as they may provide new invasion-related insights. Previously, we proved that interplay between metabolism and cytoskeleton existed in glioblastoma. Despite searching for cytoskeleton-related processes in which the investigated genes might have been involved, not only did we stumble across the relation to metabolism but also reported genes that were found to be implicated in stemness. Thus, dedicated research on these genes in GSCs seems justifiable and might reveal novel directions and/or biomarkers that could be utilized in the future. Herein, we review the previously identified cytoskeleton/metabolism-related genes through the prism of glioblastoma stemness.

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Section: Discussionmentioning

confidence: 99%

Delineating the glioblastoma stemness by genes involved in cytoskeletal rearrangements and metabolic alterations

Kałuzińska¹,

Kołat²,

Kośla³

et al. 2023

World J Stem Cells

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“…According to a previous study ( 175 ), CAR-T cell therapy poses serious problems in the treatment of central nervous system tumors, which emphasizes the problem of the hostile immunosuppressive microenvironment of CSCs. However, in addition to CAR-T cells, attempts to use CAR-T natural killer cells or CAR macrophages and to generate active antineoplastic immunity in patients with GB are of great interest.…”

Section: Hscs and Immunotherapymentioning

confidence: 99%

Regulation of cancer stem cells and immunotherapy of glioblastoma (Review)

Kosianova,

Pak,

Bryukhovetskiy

2023

Biomed Rep

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Glioblastoma (GB) is one of the most adverse diagnoses in oncology. Complex current treatment results in a median survival of 15 months. Resistance to treatment is associated with the presence of cancer stem cells (CSCs). The present review aimed to analyze the mechanisms of CSC plasticity, showing the particular role of β-catenin in regulating vital functions of CSCs, and to describe the molecular mechanisms of Wnt-independent increase of β-catenin levels, which is influenced by the local microenvironment of CSCs. The present review also analyzed the reasons for the low effectiveness of using medication in the regulation of CSCs, and proposed the development of immunotherapy scenarios with tumor cell vaccines, containing heterogenous cancer cells able of producing a multidirectional antineoplastic immune response. Additionally, the possibility of managing lymphopenia by transplanting hematopoietic stem cells from a healthy sibling and using clofazimine or other repurposed drugs that reduce β-catenin concentration in CSCs was discussed in the present study. Contents 1. Introduction 2. Principles of GB treatment 3. CC plasticity and resistance to treatment 4. Wnt signaling pathway and the microenvironment of CSCs 5. Targeted therapy and CSC plasticity 6. β-catenin inhibitors and CT 7. CSC microenvironment, immunotherapy and immunodeficiency 8. HSCs and immunotherapy 9. Conclusion

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“…In the last decade, an increasing number of immunotherapies have been developed for GBM (Yu and Quail 2021 , Bausart et al. 2022 , Bryukhovetskiy 2022 ). Anti-PD-1 is a standard immunotherapy that has proven to be beneficial in treating other cancers, such as melanoma (Postow et al.…”

Section: Introductionmentioning

confidence: 99%

Global stability and parameter analysis reinforce therapeutic targets of PD-L1-PD-1 and MDSCs for glioblastoma

Anderson,

Takacs,

Harris

et al. 2023

J. Math. Biol.

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Glioblastoma (GBM) is an aggressive primary brain cancer that currently has minimally effective treatments. Like other cancers, immunosuppression by the PD-L1-PD-1 immune checkpoint complex is a prominent axis by which glioma cells evade the immune system. Myeloid-derived suppressor cells (MDSCs), which are recruited to the glioma microenviroment, also contribute to the immunosuppressed GBM microenvironment by suppressing T cell functions. In this paper, we propose a GBM-specific tumor-immune ordinary differential equations model of glioma cells, T cells, and MDSCs to provide theoretical insights into the interactions between these cells. Equilibrium and stability analysis indicates that there are unique tumorous and tumor-free equilibria which are locally stable under certain conditions. Further, the tumor-free equilibrium is globally stable when T cell activation and the tumor kill rate by T cells overcome tumor growth, T cell inhibition by PD-L1-PD-1 and MDSCs, and the T cell death rate. Bifurcation analysis suggests that a treatment plan that includes surgical resection and therapeutics targeting immune suppression caused by the PD-L1-PD1 complex and MDSCs results in the system tending to the tumor-free equilibrium. Using a set of preclinical experimental data, we implement the approximate Bayesian computation (ABC) rejection method to construct probability density distributions that estimate model parameters. These distributions inform an appropriate search curve for global sensitivity analysis using the extended fourier amplitude sensitivity test. Sensitivity results combined with the ABC method suggest that parameter interaction is occurring between the drivers of tumor burden, which are the tumor growth rate and carrying capacity as well as the tumor kill rate by T cells, and the two modeled forms of immunosuppression, PD-L1-PD-1 immune checkpoint and MDSC suppression of T cells. Thus, treatment with an immune checkpoint inhibitor in combination with a therapeutic targeting the inhibitory mechanisms of MDSCs should be explored.

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Cell‑based immunotherapy of glioblastoma multiforme (Review)

Cited by 8 publications

References 153 publications

Delineating the glioblastoma stemness by genes involved in cytoskeletal rearrangements and metabolic alterations

Delineating the glioblastoma stemness by genes involved in cytoskeletal rearrangements and metabolic alterations

Regulation of cancer stem cells and immunotherapy of glioblastoma (Review)

Global stability and parameter analysis reinforce therapeutic targets of PD-L1-PD-1 and MDSCs for glioblastoma

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