A novel integrated system using patient-derived glioma cerebral organoids and xenografts for disease modeling and drug screening

Zhang, Liyang; Liu, Fangkun; Weygant, Nathaniel; Zhang, Junxia; Hu, Ping; Qin, Zailong; Yang, Jingxuan; Cheng, Quan; Fan, Fan; Zeng, Yu; Tang, Yongjian; Li, Yusheng; Tang, Anliu; He, Fengjiao; Peng, Jun; Liao, Weihua; Hu, Ziyi; Li, Min; Liu, Zhixiong

doi:10.1016/j.canlet.2020.12.013

Cited by 34 publications

(41 citation statements)

References 44 publications

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“…Some researchers have indicated that CALD1 expression is restricted to vessel architectures in glioma [ 11 ]. Our previous study reveals that CALD1 transcriptomic level in glioma patient-derived tumor cells (GPDCs) associating with glioma grades progression is an accompanying phenomenon [ 12 ]. In this study, we explored the role of CALD1 in gliomas by integrating bulk RNA-seq analysis and single cell RNA-seq analysis.…”

Section: Introductionmentioning

confidence: 99%

CALD1 Modulates Gliomas Progression via Facilitating Tumor Angiogenesis

Cheng

Tang

Wang

et al. 2021

Cancers

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Angiogenesis is more prominent in anaplastic gliomas and glioblastoma (GBM) than that in pilocytic and diffuse gliomas. Caldesmon (CALD1) plays roles in cell adhesion, cytoskeletal organization, and vascularization. However, limited information is available on mechanisms underlying the effect of CALD1 on the microvascular facilitation and architecture in glioma. In this study, we explored the role of CALD1 in gliomas by integrating bulk RNA-seq analysis and single cell RNA-seq analysis. A positive correlation between CALD1 expression and the gliomas’ pathological grade was noticed, according to the samples from the TCGA and CGGA database. Moreover, higher CALD1 expression samples showed worse clinical outcomes than lower CALD1 expression samples. Biofunction prediction suggested that CALD1 may affect glioma progression through modulating tumor angiogenesis. The map of the tumor microenvironment also depicted that more stromal cells, such as endothelial cells and pericytes, infiltrated in high CALD1 expression samples. CALD1 was found to be remarkably upregulated in neoplastic cells and was involved in tumorigenic processes of gliomas in single cell sequencing analysis. Histology and immunofluorescence analysis also indicated that CALD1 associates with vessel architecture, resulting in glioma grade progression. In conclusion, the present study implies that CALD1 may serve as putative marker monitoring the progress of glioma.

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Section: Introductionmentioning

confidence: 99%

CALD1 Modulates Gliomas Progression via Facilitating Tumor Angiogenesis

Cheng

Tang

Wang

et al. 2021

Cancers

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“…The system faithfully recapitulated the histological features, response to chemotherapy drugs, and clinical progression of their corresponding parental tumors. In conclusion, they developed an integrated system of parallel models from patient-derived glioma cerebral organoids and xenografts for understanding the glioma biology and prediction of response to chemotherapy drugs, which might lead to a new strategy for personalized treatment for this deadly disease [ 74 ].…”

Section: Application Of Glioma Organoidsmentioning

confidence: 99%

Opportunities and challenges of glioma organoids

Luo

et al. 2021

Cell Commun Signal

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Glioma is the most common primary brain tumor and its prognosis is poor. Despite surgical removal, glioma is still prone to recurrence because it grows rapidly in the brain, is resistant to chemotherapy, and is highly aggressive. Therefore, there is an urgent need for a platform to study the cell dynamics of gliomas in order to discover the characteristics of the disease and develop more effective treatments. Although 2D cell models and animal models in previous studies have provided great help for our research, they also have many defects. Recently, scientific researchers have constructed a 3D structure called Organoids, which is similar to the structure of human tissues and organs. Organoids can perfectly compensate for the shortcomings of previous glioma models and are currently the most suitable research platform for glioma research. Therefore, we review the three methods currently used to establish glioma organoids. And introduced how they play a role in the diagnosis and treatment of glioma. Finally, we also summarized the current bottlenecks and difficulties encountered by glioma organoids, and the current efforts to solve these difficulties.

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“…Besides genetic and epigenetic variations in glioma cells, tumor microenvironment (TME) also plays a critical role in tumor proliferation, progression, and therapeutic responses ( 4 , 5 ). TME is a complex network of cancer cells, stromal cells and, most importantly, infiltrating immune cells.…”

Section: Introductionmentioning

confidence: 99%

Immune Infiltrating Cells-Derived Risk Signature Based on Large-scale Analysis Defines Immune Landscape and Predicts Immunotherapy Responses in Glioma Tumor Microenvironment

Zhang

Wang

et al. 2021

Front. Immunol.

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The glioma tumor microenvironment (TME), composed of several noncancerous cells and biomolecules is known for its complexity of cancer-immune system interaction. Given that, novel risk signature is required for predicting glioma patient responses to immunotherapy. In this study, we systematically evaluated the TME infiltration pattern of 2877 glioma samples. TME phenotypes were determined using the Partitioning Around Medoid method. Machine learning including SVM-RFE and Principal component analysis (PCA) were used to construct a TME scoring system. A total of 857 glioma samples from four datasets were used for external validation of the TME-score. The correlation of TME phenotypes and TME-scores with diverse clinicopathologic characteristics, genomic features, and immunotherapeutic efficacy in glioma patients was determined. Immunohistochemistry staining for the M2 macrophage marker CD68 and CD163, mast cell marker CD117, neutrophil marker CD66b, and RNA sequencing of glioma samples from the XYNS cohort were performed. Two distinct TME phenotypes were identified. High TME-score correlated with a high number of immune infiltrating cells, elevated expression of immune checkpoints, increased mutation rates of oncogenes, and poor survival of glioma patients. Moreover, high TME-score exhibited remarkable association with multiple immunomodulators that could potentially mediate immune escape of cancer. Thus, the TME-score showed the potential to predict the efficacy of anti-PD-1 immunotherapy. Univariate and multivariate analyses demonstrated the TME-score to be a valuable prognostic biomarker for gliomas. Our study demonstrated that TME could potentially influence immunotherapy efficacy in melanoma patients whereas its role in immunotherapy of glioma patients remains unknown. Therefore, a better understanding of the TME landscape in gliomas would promote the development of novel immunotherapy strategies against glioma.

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A novel integrated system using patient-derived glioma cerebral organoids and xenografts for disease modeling and drug screening

Cited by 34 publications

References 44 publications

CALD1 Modulates Gliomas Progression via Facilitating Tumor Angiogenesis

CALD1 Modulates Gliomas Progression via Facilitating Tumor Angiogenesis

Opportunities and challenges of glioma organoids

Immune Infiltrating Cells-Derived Risk Signature Based on Large-scale Analysis Defines Immune Landscape and Predicts Immunotherapy Responses in Glioma Tumor Microenvironment

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