Tumour-associated macrophages exhibit anti-tumoural properties in Sonic Hedgehog medulloblastoma

Maximov, Victor; Chen, Zhihong; Wei, Yun; Robinson, M. Hope; Herting, Cameron J.; Shanmugam, Nithya; Rudneva, Vasilisa A.; Goldsmith, Kelly; MacDonald, Tobey J.; Northcott, Paul A.; Hambardzumyan, Dolores; Kenney, Anna Marie

doi:10.1038/s41467-019-10458-9

Cited by 90 publications

(96 citation statements)

References 34 publications

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“…In contrast to M2-M, NA-microglia trended toward being less abundant in SHH compared to GP3 and GP4 in scRNAseq samples (27-fold)( Figure 5E) and were significantly less abundant in SHH in the larger MAGIC cohort (4-fold, p=9.4x10 -16 )( Figure 5F). These findings are congruent with prior studies that identified a less immune active phenotype in GP3 and GP4 than SHH (Margol et al, 2015;Maximov et al, 2019). (Table S5).…”

Section: Thesupporting

confidence: 92%

Neoplastic and immune single cell transcriptomics define subgroup-specific intra-tumoral heterogeneity of childhood medulloblastoma

Riemondy

Venkataraman

Willard

et al. 2020

Preprint

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Medulloblastoma (MB) is a heterogeneous disease in which neoplastic cells and associated immune cells contribute to disease progression. To better understand cellular heterogeneity in MB we profile neoplastic and immune populations in childhood MB samples using single-cell RNA sequencing, immunohistochemistry and deconvolution of transcriptomic data. Neoplastic cells cluster primarily according to individual sample of origin which is in part due to the effect of chromosomal copy number gains and losses. Harmony alignment reveals novel MB subgroup/subtype-associated subpopulations that recapitulate neurodevelopmental processes and are associated with clinical outcomes. We identify discrete photoreceptor-like cells in MB subgroups GP3 and GP4 and nodule-associated neuronally-differentiated cells in subgroup SHH. MB immune infiltrates consist of both developmentally-related neuron-pruning and antigen presenting myeloid cells. We show that this MB cellular diversity is recapitulated in genetically engineered mouse subgroup-specific models of MB. These findings advance our understanding of both the neoplastic and immune landscape of MB.

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Section: Thesupporting

confidence: 92%

Neoplastic and immune single cell transcriptomics define subgroup-specific intra-tumoral heterogeneity of childhood medulloblastoma

Riemondy

Venkataraman

Willard

et al. 2020

Preprint

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“…With the high-speed development of omics, high-throughput tumor databases have been established, including TCGA and CGGA, which provided a solid foundation for analyzing the RNA modification and microenvironments of glioma ( 3 , 44 – 46 ). One of the emerging strategies of management is based on the roles of immune cells in the growth and maintenance of tumors ( 47 ). According to the recent studies, myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAMs) have been identified as promising targets for anti-cancer treatment ( 48 , 49 ).…”

Section: Discussionmentioning

confidence: 99%

Prognosis Analysis and Validation of m6A Signature and Tumor Immune Microenvironment in Glioma

Lin

Zhang

et al. 2020

Front. Oncol.

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Glioma is one of the most typical intracranial tumors, comprising about 80% of all brain malignancies. Several key molecular signatures have emerged as prognostic biomarkers, which indicate room for improvement in the current approach to glioma classification. In order to construct a more veracious prediction model and identify the potential prognosis-biomarker, we explore the differential expressed m 6 A RNA methylation regulators in 665 gliomas from TCGA-GBM and TCGA-LGG. Consensus clustering was applied to the m6A RNA methylation regulators, and two glioma subgroups were identified with a poorer prognosis and a higher grade of WHO classification in cluster 1. The further chi-squared test indicated that the immune infiltration was significantly enriched in cluster 1, indicating a close relation between m 6 A regulators and immune infiltration. In order to explore the potential biomarkers, the weighted gene co-expression network analysis (WGCNA), along with Least absolute shrinkage and selection operator (LASSO), between high/low immune infiltration and m 6 A cluster 1/2 groups were utilized for the hub genes, and four genes ( TAGLN2, PDPN, TIMP1, EMP3) were identified as prognostic biomarkers. Besides, a prognostic model was constructed based on the four genes with a good prediction and applicability for the overall survival (OS) of glioma patients (the area under the curve of ROC achieved 0.80 (0.76–0.83) and 0.72 (0.68–0.76) in TCGA and Chinese Glioma Genome Atlas (CGGA), respectively). Moreover, we also found PDPN and TIMP1 were highly expressed in high-grade glioma from The Human Protein Atlas database and both of them were correlated with m6A and immune cell marker in glioma tissue samples. In conclusion, we construct a novel prognostic model which provides new insights into glioma prognosis. The PDPN and TIMP1 may serve as potential biomarkers for prognosis of glioma.

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“…Moreover, we were able to construct four PPI modules, all of which were related to critical GBM biological processes. Highly relevant nodes in the modules, including STAT3, SLC11A1, and ITGAM, have been reported to promote tumor proliferation, angiogenesis, migration, and invasiveness (73)(74)(75)(76)(77). Among the 64 genes validated, 27 (such as ALOX5, CAST, HS6ST1, ITGAM, PTPN6, SLC11A1, and SLC12A7) have been reported to be involved in the pathogenesis of GBM or critical in predicting OS.…”

Section: Discussionmentioning

confidence: 99%

Malignant Evaluation and Clinical Prognostic Values of m6A RNA Methylation Regulators in Glioblastoma

Du¹,

Hou²,

Mi³

et al. 2020

Front. Oncol.

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N6-methyladenosine (m6A) RNA methylation, the most common form of mRNA modification and regulated by the m6A RNA methylation regulators ("writers," "erasers," and "readers"), has been reported to be associated with the progression of the malignant tumor. However, its role in glioblastoma (GBM) has been poorly known. This study aimed to identify the expression, potential functions, and prognostic values of m6A RNA methylation regulators in GBM. Here, we revealed that the 13 central m6A RNA methylation regulators were firmly related to the clinical and molecular phenotype of GBM. Taking advantage of consensus cluster analysis, we obtained two categories of GBM samples and found malignancy-related processes of m6A methylation regulators and compounds that specifically targeted the malignant processes. Besides, we also obtained a list of genes with poor prognosis in GBM. Finally, we derived a risk-gene signature with three selected m6A RNA methylation regulators, which allowed us to extend the in-depth study and dichotomized the OS of patients with GBM into high-and low-risk subgroups. Notably, this risk-gene signature could be used as independent prognostic markers and accurate clinicopathological parameter predictors. In conclusion, m6A RNA methylation regulators are a type of vital participant in the malignant progression of GBM, with a critical potential in the prognostic stratification and treatment strategies of GBM.

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Tumour-associated macrophages exhibit anti-tumoural properties in Sonic Hedgehog medulloblastoma

Cited by 90 publications

References 34 publications

Neoplastic and immune single cell transcriptomics define subgroup-specific intra-tumoral heterogeneity of childhood medulloblastoma

Neoplastic and immune single cell transcriptomics define subgroup-specific intra-tumoral heterogeneity of childhood medulloblastoma

Prognosis Analysis and Validation of m6A Signature and Tumor Immune Microenvironment in Glioma

Malignant Evaluation and Clinical Prognostic Values of m6A RNA Methylation Regulators in Glioblastoma

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