Heterogeneity of glioblastoma stem cells in the context of the immune microenvironment and geospatial organization

Silver, Aryeh; Feier, Diana; Ghosh, Tanya; Rahman, Maryam; Huang, Jianping; Sarkisian, Matthew R.; Deleyrolle, Loic P.

doi:10.3389/fonc.2022.1022716

Cited by 15 publications

(20 citation statements)

References 271 publications

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“…GAMs and GSCs are often functionally interconnected and co-localized. Mapping of cellular distribution in human GBM revealed that striking numbers of GAMs were located around GSC clusters and, as observed with GAMS, the density of GSCs positively correlated to tumor grade ( 40 ). GAMs accumulate in perivascular regions where they produce proangiogenic factors such as VEGF and CXCL2, due to chemoattractant release from GSCs ( 36 ).…”

Section: Gams In the Gbm Microenvironmentmentioning

confidence: 87%

“…In the presence of glioma cells, microglia produce significant amounts of TGF-β, which in turn induces production of matrix metalloproteinase 9 (MMP9) and MMP2, leading to degradation of ECM and supporting glioma stem cell invasion ( 38 ). GSCs are treatment resistant, multipotent, self-renewing cells with high heterogeneity ( 39 , 40 ). GAMs and GSCs are often functionally interconnected and co-localized.…”

Section: Gams In the Gbm Microenvironmentmentioning

confidence: 99%

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Pleiotropic effects of the COX-2/PGE2 axis in the glioblastoma tumor microenvironment

Dean

Hooks

2023

Front. Oncol.

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Glioblastoma (GBM) is the most common and aggressive form of malignant glioma. The GBM tumor microenvironment (TME) is a complex ecosystem of heterogeneous cells and signaling factors. Glioma associated macrophages and microglia (GAMs) constitute a significant portion of the TME, suggesting that their functional attributes play a crucial role in cancer homeostasis. In GBM, an elevated GAM population is associated with poor prognosis and therapeutic resistance. Neoplastic cells recruit these myeloid populations through release of chemoattractant factors and dysregulate their induction of inflammatory programs. GAMs become protumoral advocates through production a variety of cytokines, inflammatory mediators, and growth factors that can drive cancer proliferation, invasion, immune evasion, and angiogenesis. Among these inflammatory factors, cyclooxygenase-2 (COX-2) and its downstream product, prostaglandin E2 (PGE2), are highly enriched in GBM and their overexpression is positively correlated with poor prognosis in patients. Both tumor cells and GAMs have the ability to signal through the COX-2 PGE2 axis and respond in an autocrine/paracrine manner. In the GBM TME, enhanced signaling through the COX-2/PGE2 axis leads to pleotropic effects that impact GAM dynamics and drive tumor progression.

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Section: Gams In the Gbm Microenvironmentmentioning

confidence: 87%

Section: Gams In the Gbm Microenvironmentmentioning

confidence: 99%

Pleiotropic effects of the COX-2/PGE2 axis in the glioblastoma tumor microenvironment

Dean

Hooks

2023

Front. Oncol.

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“…29 Multiple lines of evidence suggest that TAMs have a role in promoting tumorigenesis, growth, invasion, and metastasis, affecting tumor metabolism. 30,31 Microhabitat maintains the essential properties of glioma stem cells, maintaining their phenotypic plasticity and thus allowing them to effectively evade surveillance by the immune system. 32 Recently single-cell analysis has emerged as a powerful tool to study the heterogeneity of gliomas at the single-cell level and to identify the cellular and molecular mechanisms involved in immune escape.…”

Section: The Overvie W Of G LI Oma Tumor Immune Micro Env Iro Nmentmentioning

confidence: 99%

“…In the stem cell microenvironment, glioma stem cells can induce differentiation of bone marrow‐derived monocytes and microglia into TAMs, the latter being the major inflammatory cell population in the TME 29 . Multiple lines of evidence suggest that TAMs have a role in promoting tumorigenesis, growth, invasion, and metastasis, affecting tumor metabolism 30,31 . Microhabitat maintains the essential properties of glioma stem cells, maintaining their phenotypic plasticity and thus allowing them to effectively evade surveillance by the immune system 32 …”

Section: The Overview Of Glioma Tumor Immune Microenvironmentmentioning

confidence: 99%

Advances in research on immune escape mechanism of glioma

Guo

Wang

2023

CNS Neurosci Ther

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Background Glioma is the most common primary intracranial malignancy in clinical practice, and in particular, IDH‐wildtype glioblastoma has the worst prognosis. In recent years, surgical resection combined with simultaneous radiotherapy and immune checkpoint inhibitors has made some progress, but the efficacy is still not satisfactory, which may be related to the low immunogenicity of glioma cells and the tumor immunosuppressive microenvironment. Methods A comprehensive review of relevant literature was conducted to explore the mechanisms by which tumors suppress antitumor immune responses and produce escape, with a focus on the immune cells in the tumor microenvironment (TME). Results The mechanisms involved in immune evasion of glioma cells are complex and involve with immune cell differentiation and function. Conclusion Our review emphasizes the need for a more profound comprehension of the mechanisms involved in immune response and immune evasion in glioma, to formulate more efficacious treatment modalities.

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“…These results support the efficacy of this assay in more closely recapitulating the human disease as compared to KR158 cells cultured in adherent monolayer serum-containing conditions. Our previous research established the existence of a metabolic diversity within the microenvironment of human GBM, which includes fast and slow cycling cells with distinct metabolic features 1,5,16,19 . Moreover, SCCs isolated from human GBM tumors have demonstrated increased stemness, enhanced invasion, and drug resistance, pointing to their role in tumor progression and recurrence 16,19,20 .…”

Section: Introductionmentioning

confidence: 98%

KR158 spheres harboring slow-cycling cells recapitulate GBM features in an immunocompetent system

Chakraborty,

Yang,

Kresak

et al. 2024

Preprint

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Glioblastoma (GBM) poses a significant challenge in clinical oncology due to its aggressive nature, heterogeneity, and resistance to therapies. Cancer stem cells (CSCs) play a critical role in GBM, particularly in treatment-resistance and tumor relapse, emphasizing the need to comprehend the mechanisms regulating these cells. Also, their multifaceted contributions to the tumor-microenvironment (TME) underline their significance, driven by their unique properties. This study aimed to characterize glioblastoma stem cells (GSCs), specifically slow-cycling cells (SCCs), in an immunocompetent murine GBM model to explore their similarities with their human counterparts. Using the KR158 mouse model, we confirmed that SCCs isolated from this model exhibited key traits and functional properties akin to human SCCs. KR158 murine SCCs, expanded in the gliomasphere assay, demonstrated sphere forming ability, self-renewing capacity, positive tumorigenicity, enhanced stemness and resistance to chemotherapy. Together, our findings validate the KR158 murine model as a framework to investigate GSCs and SCCs in GBM-pathology, and explore specifically the SCC-immune system communications, understand their role in disease progression, and evaluate the effect of therapeutic strategies targeting these specific connections.

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Heterogeneity of glioblastoma stem cells in the context of the immune microenvironment and geospatial organization

Cited by 15 publications

References 271 publications

Pleiotropic effects of the COX-2/PGE2 axis in the glioblastoma tumor microenvironment

Pleiotropic effects of the COX-2/PGE2 axis in the glioblastoma tumor microenvironment

Advances in research on immune escape mechanism of glioma

KR158 spheres harboring slow-cycling cells recapitulate GBM features in an immunocompetent system

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