Tumor Microenvironment Is Critical for the Maintenance of Cellular States Found in Primary Glioblastomas

Pine, Allison R.; Cirigliano, Stéfano M.; Nicholson, James; Hu, Yang; Linkous, Amanda; Miyaguchi, Ken; Edwards, Lincoln; Singhania, Richa; Schwartz, Theodore H.; Ramakrishna, Rohan; Pisapia, David; Snuderl, Matija; Elemento, Olivier; Fine, Howard A.

doi:10.1158/2159-8290.cd-20-0057

Cited by 125 publications

(141 citation statements)

References 37 publications

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“…The major non-neoplastic immune cell population in the GBM microenvironment includes cells of the innate immune system called tumor-associated macrophages (TAMs), as well as the stromal cells such as tumor-associated broblasts (TAFs). TAMs and TAFs are of great importance in several aspects of the tumor progression and chemotherapeutic processes of GBM [10]. It's been reported that age-related immune alternations could cause landscape remodeling of the tumor microenvironment and initiate the invasiveness and aggressiveness of tumors, including GBM [41].…”

Section: Discussionmentioning

confidence: 99%

“…Intracellular heterogeneity allows the classi cation of these tumors into different molecular subtypes, namely proneural (PN), classical (CL) and mesenchymal (MES) subtypes, among which MES had the poorest outcome [7]. Intercellular heterogeneity, on the other side, contains a series of non-neoplastic cells, including in ltrating and resident immune cells, stromal cells, other glial cells, extracellular matrices (ECM) and other components related to the tumor microenvironment (TME) [10]. This tumor immunology and tumor microenvironment has added another level of complexity to this phenomenon.…”

Section: Backgroundsmentioning

confidence: 99%

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WITHDRAWN: Aging-related tumor microenvironment changes could worsen the prognosis of GBM patients

Song

et al. 2020

Preprint

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Background: Glioblastoma multiforme (GBM) is the most malignant tumor in human brain, with highly heterogeneity among different patients. Age could function as an incidence and prognosis risk factor for many tumors.Method: A series of bioinformatic experiments were conducted to evaluate the differences of incidence, differential expressed genes, enriched pathways with the data from Surveillance, Epidemiology, and End Results (SEER) program, the cancer genome atlas (TCGA) and Chinese glioma genome atlas (CGGA) project.Results: We discovered in our present study that distinct difference of incidence and prognosis of different aged GBM patients. By a series of bioinformatic method, we found that the tumor associated fibroblasts (TAFs) was the most crucial tumor microenvironment (TME) component that led to this phenomenon. Epithelial-mesenchymal transition (EMT) could be the mechanism by which TAFs regulate the progression of GBM. Conclusion: We have proposed a close correlation between age and GBM incidence and prognosis, and propose the underlying mechanism behind this correlation by mining different databases, which laid the foundation for future research.

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Section: Discussionmentioning

confidence: 99%

Section: Backgroundsmentioning

confidence: 99%

WITHDRAWN: Aging-related tumor microenvironment changes could worsen the prognosis of GBM patients

Song

et al. 2020

Preprint

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“…Furthermore, GBM has been extensively characterized by scRNA-seq providing a detailed baseline for both the transformed populations that co-occur in individual patients and the microenvironment [7][8][9][10][11] . Indeed, single-cell characterization of GBM models has highlighted the importance of the tumor microenvironment in maintaining the phenotypic diversity of malignant cells 12 . We obtained GBM surgical specimens from six patients, generated multiple 500 micron slices, and placed them in short-term culture for drug perturbation (Fig.…”

mentioning

confidence: 99%

Deconvolution of Cell Type-Specific Drug Responses in Human Tumor Tissue with Single-Cell RNA-seq

Zhao

Dovas

Spinazzi

et al. 2020

Preprint

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Precision oncology requires the timely selection of effective drugs for individual patients. An ideal platform would enable rapid screening of cell type-specific drug sensitivities directly in patient tumor tissue and reveal strategies to overcome intratumoral heterogeneity. Here we combine multiplexed drug perturbation in acute slice culture from freshly resected tumors with single-cell RNA sequencing (scRNA-seq) to profile transcriptome-wide drug responses. We applied this approach to glioblastoma (GBM) and demonstrated that acute slice cultures from individual patients recapitulate the cellular and molecular features of the originating tumor tissue. Detailed investigation of etoposide, a topoisomerase poison, and the histone deacetylase (HDAC) inhibitor panobinostat in acute slice cultures revealed cell type-specific responses across multiple patients, including unexpected effects on the immune microenvironment. We anticipate that this approach will facilitate rapid, personalized drug screening to identify effective therapies for solid tumors.Inter-and intra-tumoral heterogeneity present major challenges for cancer therapy. Precision medicine, or targeted therapy, entails the use of agents that preferentially target tumor cells based on unique molecular features. The success of this approach relies on extensive characterization of tumor heterogeneity and microenvironment. While scRNA-seq can determine the cellular composition of complex tumors and even reveal cell type-specific drug sensitivities, these measurements are ultimately limited by models of

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“…We found that those GBM patients with higher PHQ-9 and GAD-7 score have signi cantly worse prognosis than their lower scored counterparts. It seems the case that glioblastoma and depressive/anxiety disorder share some common etiological factors, such as in ammation [33,34], neurotransmitter metabolism [35], glutamine [36,37], neural plasticity [38,39], etc. Nevertheless, none of these factors were con rmed by further research.…”

Section: Discussionmentioning

confidence: 99%

LTBP1 plays a potential bridge between depressive disorder and glioblastoma

Zhang

Song³

et al. 2020

Preprint

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Background: Glioblastoma multiforme (GBM) is the most malignant tumor in human brain. Diagnosis and treatment of GBM may lead to psychological disorders such as depressive and anxiety disorders. There was no research focusing on the correlation between depressive/anxiety disorder and the outcome of GBM. Thus, the aim of this study was to investigate the possibility of depressive/anxiety disorder correlated with the outcome of GBM patients, as well as the overlapped mechanism bridge which could link depressive/anxiety disorders and GBM.Methods: Patient Health Questionnaire (PHQ-9) and Generalized Anxiety Disorder (GAD-7) were used to investigate the psychological condition of GBM patients in our department. To further explore the potential mechanism, bioinformatic methods were used to screen out genes that could be indicators of outcome in GBM, followed by gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and protein-protein interaction (PPI) analysis. Further, cellular experiments were conducted to evaluate the proliferation, migration capacity of primary GBM cells from the patients.Results: It was revealed that patients with higher PHQ-9 and GAD-7 scores had significantly worse prognosis than their lower-scored counterparts. Bioinformatic mining revealed that LTBP1 could be a potential genetic mechanism in both depressive/anxiety disorder and GBM. Primary GBM cells with different expression level of LTBP1 should significantly different proliferation and migration capacity. GO, KEGG analysis confirmed that extracellular matrix (ECM) was the most enriched function of LTBP1. PPI network showed the interaction of proteins altered by LTBP1. Hub genes COL1A2, COL5A1 and COL10A1, as well as mesenchymal marker CD44 and Vimentin were statistically higher expressed in LTBP1 high group; while proneural marker E-cadherin was significantly higher expressed in low LTBP1 group.Conclusion: There is closely correlation between depressive/anxiety disorders and GBM. LTBP1 could be a potential bridge linking the two diseases through the regulation of ECM.

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Tumor Microenvironment Is Critical for the Maintenance of Cellular States Found in Primary Glioblastomas

Abstract: Tumor microenvironment is critical for the maintenance of cellular states found in primary glioblastomas.

Cited by 125 publications

References 37 publications

WITHDRAWN: Aging-related tumor microenvironment changes could worsen the prognosis of GBM patients

WITHDRAWN: Aging-related tumor microenvironment changes could worsen the prognosis of GBM patients

Deconvolution of Cell Type-Specific Drug Responses in Human Tumor Tissue with Single-Cell RNA-seq

LTBP1 plays a potential bridge between depressive disorder and glioblastoma

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