Differential Expression and Clinical Significance of Transforming Growth Factor-Beta Isoforms in GBM Tumors

Roy, Laurent-Olivier; Poirier, Marie-Belle; Fortin, David

doi:10.3390/ijms19041113

Cited by 42 publications

(44 citation statements)

References 46 publications

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“…Members of the TGF-β family are highly expressed in GBM, and are important in maintaining the GSC pool [25]. Furthermore, we and others have previously shown that TGF-β reduces the expression of NKp30, NKG2D and DNAM-1 on NK cells and is associated with their functional inactivation [26,27].…”

Section: (A) (B)mentioning

confidence: 71%

Expression profiling of single cells and patient cohorts identifies multiple immunosuppressive pathways and an altered NK cell phenotype in glioblastoma

Stead

Nsengimana

et al. 2019

Clinical and Experimental Immunology

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Summary Glioblastoma (GBM) is an aggressive cancer with a very poor prognosis. Generally viewed as weakly immunogenic, GBM responds poorly to current immunotherapies. To understand this problem more clearly we used a combination of natural killer (NK) cell functional assays together with gene and protein expression profiling to define the NK cell response to GBM and explore immunosuppression in the GBM microenvironment. In addition, we used transcriptome data from patient cohorts to classify GBM according to immunological profiles. We show that glioma stem‐like cells, a source of post‐treatment tumour recurrence, express multiple immunomodulatory cell surface molecules and are targeted in preference to normal neural progenitor cells by natural killer (NK) cells ex vivo. In contrast, GBM‐infiltrating NK cells express reduced levels of activation receptors within the tumour microenvironment, with hallmarks of transforming growth factor (TGF)‐β‐mediated inhibition. This NK cell inhibition is accompanied by expression of multiple immune checkpoint molecules on T cells. Single‐cell transcriptomics demonstrated that both tumour and haematopoietic‐derived cells in GBM express multiple, diverse mediators of immune evasion. Despite this, immunome analysis across a patient cohort identifies a spectrum of immunological activity in GBM, with active immunity marked by co‐expression of immune effector molecules and feedback inhibitory mechanisms. Our data show that GBM is recognized by the immune system but that anti‐tumour immunity is restrained by multiple immunosuppressive pathways, some of which operate in the healthy brain. The presence of immune activity in a subset of patients suggests that these patients will more probably benefit from combination immunotherapies directed against multiple immunosuppressive pathways.

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Section: (A) (B)mentioning

confidence: 71%

Expression profiling of single cells and patient cohorts identifies multiple immunosuppressive pathways and an altered NK cell phenotype in glioblastoma

Stead

Nsengimana

et al. 2019

Clinical and Experimental Immunology

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“…The ROS-induced signaling pathways, viz. EGFR, MAP kinase, 103,104 TGFβ, 60,105 and NF-kB, 106,107 aid tumor development and progression as also participate in tissue repair, regeneration, and the healing processes in the postischemic recovery phase. ROS can also activate ERK1/2 signaling in glioma.…”

Section: Ros Favor Tumor Growthmentioning

confidence: 99%

The interrelationship between cerebral ischemic stroke and glioma: a comprehensive study of recent reports

Ghosh

Chakraborty

Sarkar

et al. 2019

Sig Transduct Target Ther

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Glioma and cerebral ischemic stroke are two major events that lead to patient death worldwide. Although these conditions have different physiological incidences,~10% of ischemic stroke patients develop cerebral cancer, especially glioma, in the postischemic stages. Additionally, the high proliferation, venous thrombosis and hypercoagulability of the glioma mass increase the significant risk of thromboembolism, including ischemic stroke. Surprisingly, these events share several common pathways, viz. hypoxia, cerebral inflammation, angiogenesis, etc., but the proper mechanism behind this co-occurrence has yet to be discovered. The hypercoagulability and presence of the D-dimer level in stroke are different in cancer patients than in the noncancerous population. Other factors such as atherosclerosis and coagulopathy involved in the pathogenesis of stroke are partially responsible for cancer, and the reverse is also partially true. Based on clinical and neurosurgical experience, the neuronal structures and functions in the brain and spine are observed to change after a progressive attack of ischemia that leads to hypoxia and atrophy. The major population of cancer cells cannot survive in an adverse ischemic environment that excludes cancer stem cells (CSCs). Cancer cells in stroke patients have already metastasized, but early-stage cancer patients also suffer stroke for multiple reasons. Therefore, stroke is an early manifestation of cancer. Stroke and cancer share many factors that result in an increased risk of stroke in cancer patients, and vice-versa. The intricate mechanisms for stroke with and without cancer are different. This review summarizes the current clinical reports, pathophysiology, probable causes of co-occurrence, prognoses, and treatment possibilities.

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“…Alteration in core signaling pathways in GBM genetic profiling, such as RTK/RAS/PI3K/PTEN, P53/ARF/MDM2, and RB/DKN2A pathways, drives the existence of GBM heterogeneity, which causes the recurrence of GBM. [3][4][5] Among these pathways, epidermal growth factor receptor (EGFR) is one of the most critical nodes; EGFR variant III (EGFRvIII, EGFR type III, or ΔEGFR) is the most commonly overexpressed EGFR family member in GBM, which causes tumor proliferation. 4,6 Previous studies have demonstrated that the expression of EGFRvIII is closely correlated with the poor prognosis and resistance of therapy.…”

Section: Introductionmentioning

confidence: 99%

<p>Aptamer-Conjugated Gold Nanoparticles Targeting Epidermal Growth Factor Receptor Variant III for the Treatment of Glioblastoma</p>

Peng¹,

Liang²,

Zhong³

et al. 2020

IJN

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In this study, we constructed novel brain-targeting complexes (U2-AuNP) by conjugating aptamer U2 to the gold nanoparticle (AuNPs) surface as a promising option for GBM therapy. Materials and Methods: The properties of the U2-AuNP complexes were thoroughly characterized. Then, we detected the in vitro effects of U2-AuNP in U87-EGFRvIII cell lines and the in vivo antitumor effects of U2-AuNP in GBM-bearing mice. Furthermore, we explored the inhibition mechanism of U2-AuNP in U87-EGFRvIII cell lines. Results: We found that U2-AuNP inhibits the proliferation and invasion of U87-EGFRvIII cell lines and prolongs the survival time of GBM-bearing mice. We found that U2-AuNP can inhibit the EGFR-related pathway and prevent DNA damage repair in GBM cells. Conclusion: These results reveal the promising potential of U2-AuNP as a drug candidate for targeted therapy in GBM.

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Differential Expression and Clinical Significance of Transforming Growth Factor-Beta Isoforms in GBM Tumors

Cited by 42 publications

References 46 publications

Expression profiling of single cells and patient cohorts identifies multiple immunosuppressive pathways and an altered NK cell phenotype in glioblastoma

Expression profiling of single cells and patient cohorts identifies multiple immunosuppressive pathways and an altered NK cell phenotype in glioblastoma

The interrelationship between cerebral ischemic stroke and glioma: a comprehensive study of recent reports

<p>Aptamer-Conjugated Gold Nanoparticles Targeting Epidermal Growth Factor Receptor Variant III for the Treatment of Glioblastoma</p>

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