Adverse prognosis of glioblastoma contacting the subventricular zone: Biological correlates

Berendsen, Sharon; Bodegraven, Emma J. van; Seute, Tatjana; Spliet, Wim G.M.; Geurts, Marjolein; Hendrikse, Jeroen; Schoysman, Laurent; Huiszoon, Willemijn B; Varkila, Meri R. J.; Rouss, Soufyan; Bell, Erica H.; Kroonen, Jérôme; Chakravarti, Arnab; Bours, Vincent; Snijders, Tom J.; Robe, Pierre A.

doi:10.1371/journal.pone.0222717

Cited by 35 publications

(52 citation statements)

References 57 publications

(72 reference statements)

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“…demonstrated that the subventricular zone of the brain can modulate GBM microenvironment and take part in MES transformation through C/EBP‐ β signaling. [ 52 ] Another study reported that transglutaminase 2 (TGM2) can act as a mediator of mesenchymal transformation in perinecrotic regions of GBM by inducing C/EBP‐ β expression through GADD153 (a transcriptional inhibitor of C/EBP β signaling) degradation. [ 53 ] Accumulating evidence demonstrated the role of STAT3 in PMT.…”

Section: Molecular Mechanisms Of Mesenchymal Transformation In Gbmmentioning

confidence: 99%

Mesenchymal Transformation: The Rosetta Stone of Glioblastoma Pathogenesis and Therapy Resistance

Azam

Tannous

2020

Advanced Science

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Despite decades of research, glioblastoma (GBM) remains invariably fatal among all forms of cancers. The high level of inter-and intratumoral heterogeneity along with its biological location, the brain, are major barriers against effective treatment. Molecular and single cell analysis identifies different molecular subtypes with varying prognosis, while multiple subtypes can reside in the same tumor. Cellular plasticity among different subtypes in response to therapies or during recurrence adds another hurdle in the treatment of GBM. This phenotypic shift is induced and sustained by activation of several pathways within the tumor itself, or microenvironmental factors. In this review, the dynamic nature of cellular shifts in GBM and how the tumor (immune) microenvironment shapes this process leading to therapeutic resistance, while highlighting emerging tools and approaches to study this dynamic double-edged sword are discussed.

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Section: Molecular Mechanisms Of Mesenchymal Transformation In Gbmmentioning

confidence: 99%

Mesenchymal Transformation: The Rosetta Stone of Glioblastoma Pathogenesis and Therapy Resistance

Azam

Tannous

2020

Advanced Science

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“…Two of them demonstrate a correlation with increased glioblastoma expression of CD133, a glioma stem cell marker, with proximity to the VSVZ (20,21). However, large bulk tissue analyses have not revealed a consistent molecular signature of VSVZ-contacting glioblastomas (9,10). Therefore, the role of the microenvironment of the VSVZ is also being probed to understand the increased malignancy of glioblastomas with VSVZ contact.…”

Section: Discussionmentioning

confidence: 99%

“…Glioblastomas with and without VSVZ invasion or contact are not genomically distinct in bulk profiling (9,10). Therefore, the more severe clinical phenotype of those patients is likely due t o t h e m i c r o e n v i r o n m e n t o f t h e V S V Z ( 9 ) .…”

Section: Introductionmentioning

confidence: 99%

Glioblastoma Distance From the Subventricular Neural Stem Cell Niche Does Not Correlate With Survival

et al. 2020

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ObjectiveTo determine the relationship between survival and glioblastoma distance from the ventricular-subventricular neural stem cell niche (VSVZ).Methods502 pre-operative gadolinium-enhanced, T1-weighted MRIs with glioblastoma retrieved from an institutional dataset (n = 252) and The Cancer Imaging Atlas (n=250) were independently reviewed. The shortest distance from the tumor contrast enhancement to the nearest lateral ventricular wall, the location of the VSVZ, was measured (GBM-VSVZDist). The relationship of GBM-VSVZDist with the proportion of glioblastomas at each distance point and overall survival was explored with a Pearson’s correlation and Cox regression model, respectively, adjusting for the well-established glioblastoma prognosticators.Results244/502 glioblastomas had VSVZ contact. The proportion of non-VSVZ-contacting glioblastomas correlated inversely with GBM-VSVZDist (partial Pearson’s correlation adjusted for tumor volume R=-0.79, p=7.11x10-7). A fit of the Cox regression model adjusted for age at diagnosis, Karnofsky performance status score, post-operative treatment with temozolomide and/or radiotherapy, IDH1/2 mutation status, MGMT promoter methylation status, tumor volume, and extent of resection demonstrated a significantly decreased overall survival only when glioblastoma contacted the VSVZ. Overall survival did not correlate with GBM-VSVZDist.ConclusionsIn the two independent cohorts analyzed, glioblastomas at diagnosis were found in close proximity or in contact with the VSVZ with a proportion that decreased linearly with GBM-VSVZDist. Patient survival was only influenced by the presence or absence of a gadolinium-enhanced glioblastoma contact with the VSVZ. These results may guide analyses to test differential effectiveness of VSVZ radiation in VSVZ-contacting and non-contacting glioblastomas and/or inform patient selection criteria in clinical trials of glioblastoma radiation.

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“…Interestingly, Hallaert et al [ 80 ] also observed that the connection of GBM to the sub-ventricular zone appears to be a novel, independent risk factor leading to a worse prognosis. An association between sub-ventricular zone contact and markers related to the epithelial–mesenchymal transition was discovered [ 81 ]. Moreover, there is a definite influence of the tumor and the response to treatment on the systemic immune and inflammatory compartments [ 34 ].…”

Section: Immunotherapy For Gbmmentioning

confidence: 99%

Randomized Controlled Immunotherapy Clinical Trials for GBM Challenged

Gool

Makalowski

Fiore

et al. 2020

Cancers

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Immunotherapies represent a promising strategy for glioblastoma multiforme (GBM) treatment. Different immunotherapies include the use of checkpoint inhibitors, adoptive cell therapies such as chimeric antigen receptor (CAR) T cells, and vaccines such as dendritic cell vaccines. Antibodies have also been used as toxin or radioactive particle delivery vehicles to eliminate target cells in the treatment of GBM. Oncolytic viral therapy and other immunogenic cell death-inducing treatments bridge the antitumor strategy with immunization and installation of immune control over the disease. These strategies should be included in the standard treatment protocol for GBM. Some immunotherapies are individualized in terms of the medicinal product, the immune target, and the immune tumor–host contact. Current individualized immunotherapy strategies focus on combinations of approaches. Standardization appears to be impossible in the face of complex controlled trial designs. To define appropriate control groups, stratification according to the Recursive Partitioning Analysis classification, MGMT promotor methylation, epigenetic GBM sub-typing, tumor microenvironment, systemic immune functioning before and after radiochemotherapy, and the need for/type of symptom-relieving drugs is required. Moreover, maintenance of a fixed treatment protocol for a dynamic, deadly cancer disease in a permanently changing tumor–host immune context might be inappropriate. This complexity is illustrated using our own data on individualized multimodal immunotherapies for GBM. Individualized medicines, including multimodal immunotherapies, are a rational and optimal yet also flexible approach to induce long-term tumor control. However, innovative methods are needed to assess the efficacy of complex individualized treatments and implement them more quickly into the general health system.

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Adverse prognosis of glioblastoma contacting the subventricular zone: Biological correlates

Cited by 35 publications

References 57 publications

Mesenchymal Transformation: The Rosetta Stone of Glioblastoma Pathogenesis and Therapy Resistance

Mesenchymal Transformation: The Rosetta Stone of Glioblastoma Pathogenesis and Therapy Resistance

Glioblastoma Distance From the Subventricular Neural Stem Cell Niche Does Not Correlate With Survival

Randomized Controlled Immunotherapy Clinical Trials for GBM Challenged

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