Medulloblastoma—Biology and Microenvironment:<i>A Review</i>

Byrd, Tiara; Grossman, Robert G.; Ahmed, Nabil

doi:10.3109/08880018.2012.698372

Cited by 10 publications

(11 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…T cells in the microenvironment and their impact on tumor growth may depend heavily upon the particular TIL subset. The majority of CD4+ T cells favor tumor progression, while CD8+ T cells favor tumor rejection ( 91 ). As mentioned above, Tregs inhibit the effect of T cells to tumor or foreign antigens ( 92 ).…”

Section: Limitations Of Cellular Therapeuticsmentioning

confidence: 99%

Adoptive Cell Therapies for Glioblastoma

2013

Self Cite

View full text Add to dashboard Cite

Glioblastoma (GBM) is the most common and most aggressive primary brain malignancy and, as it stands, is virtually incurable. With the current standard of care, maximum feasible surgical resection followed by radical radiotherapy and adjuvant temozolomide, survival rates are at a median of 14.6 months from diagnosis in molecularly unselected patients (1). Collectively, the current knowledge suggests that the continued tumor growth and survival is in part due to failure to mount an effective immune response. While this tolerance is subtended by the tumor being utterly “self,” it is to a great extent due to local and systemic immune compromise mediated by the tumor. Different cell modalities including lymphokine-activated killer cells, natural killer cells, cytotoxic T lymphocytes, and transgenic chimeric antigen receptor or αβ T cell receptor grafted T cells are being explored to recover and or redirect the specificity of the cellular arm of the immune system toward the tumor complex. Promising phase I/II trials of such modalities have shown early indications of potential efficacy while maintaining a favorable toxicity profile. Efficacy will need to be formally tested in phase II/III clinical trials. Given the high morbidity and mortality of GBM, it is imperative to further investigate and possibly integrate such novel cell-based therapies into the current standards-of-care and herein we collectively assess and critique the state-of-the-knowledge pertaining to these efforts.

show abstract

Section: Limitations Of Cellular Therapeuticsmentioning

confidence: 99%

Adoptive Cell Therapies for Glioblastoma

2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…Components of TME comprising tumour cells, immune cells and other stromal cells along with their vital interactions contribute to treatment response and disease prognosis. Accumulating evidence in both epithelial [13][14][15][16] and neural cancers [17,18] suggest a close interplay between the tumour and niche involving non-neoplastic components to secrete signalling molecules, growth factors that contribute to increased angiogenesis, invasion, progression and metastasis [19][20][21][22][23]. The TME components are hence referred to as "partners in crime" for the tumourigenesis process [24,25].…”

Section: Doi: 101159/000488709mentioning

confidence: 99%

Evidence of Tumour Microenvironment and Stromal Cellular Components in Retinoblastoma

et al. 2018

View full text Add to dashboard Cite

Background: The tumour microenvironment (TME) consisting of tumour cells and multiple stromal cell types regulate tumour growth, invasion and metastasis. While the concept of TME and presence of stromal cellular components is widely established in cancers, its significance in the paediatric intraocular malignancy, retinoblastoma (RB), remains unknown. Methods: The study qualitatively identified the presence of multiple stromal cellular subtypes in RB TME by immunohistochemistry. Results: Results of the study identified the presence of stromal cell types such as endothelial cells, tumour-associated macrophages, fibroblasts, cancer-associated fibroblasts, retinal astrocytes and glia in RB TME. The extent of stromal marker positivity, however, did not correlate with histopathological features of RB. Conclusions: The findings of the study convincingly suggest the presence of a stromal component in RB tumours. The interactions between stromal cells and tumour cells might be of profound importance in RB progression.

show abstract

“…Studies have suggested the vital role of tumor microenvironments that normally operate to regulate various types of protein stabilities during CSCs self-proliferation (45). CSCs are "clever" enough to modify the microenvironment by recruiting agents to make others, including vessels, astrocytes, fibroblasts, etc., serve themselves with the goal of maintaining self-renewal (46). For example, in medulloblastoma, GFAP þ staining represents that a few astrocytes in tumor microenvironment are activated in human and mouse model tissues ( Fig.…”

Section: Discussionmentioning

confidence: 99%

MELK and EZH2 Cooperate to Regulate Medulloblastoma Cancer Stem-like Cell Proliferation and Differentiation

Liu

Sun

et al. 2017

Molecular Cancer Research

View full text Add to dashboard Cite

Medulloblastoma is the most common malignant brain tumor in children. Although accumulated research has suggested that cancer stem-like cells play a key role in medulloblastoma tumorigenesis, the specific molecular mechanism regarding proliferation remains elusive. Here, we reported more abundant expression of maternal embryonic leucine-zipper kinase (MELK) and enhancer of zeste homolog 2 (EZH2) in medulloblastoma stemlike cells than in neural stem cells and the interaction between the two proteins could mediate the self-renewal of sonic hedgehog subtype medulloblastoma. In human medulloblastoma, extensive nodularity and large-cell/anaplastic subgroups differed according to the staining levels of MELK and EZH2 from the other two subgroups. The proportion of MELK-or EZH2-positive staining status could be considered as a potential indicator for survival. Mechanistically, MELK bound to and phosphorylated EZH2, and its methylation was induced by EZH2 in medulloblastoma, which could regulate the proliferation of cancer stemlike cells. In xenografts, loss of MELK or EZH2 attenuated medulloblastoma stem-like cell-derived tumor growth and promoted differentiation. These findings indicate that MELK-induced phosphorylation and EZH2-mediated methylation in MELK/EZH2 pathway are essential for medulloblastoma stem-like cell-derived tumor proliferation, thereby identifying a potential therapeutic strategy for these patients.Implications: This study demonstrates that the interaction occurring between MELK and EZH2 promotes self-proliferation and stemness, thus representing an attractive therapeutic target and potential candidate for diagnosis of medulloblastoma.Mol Cancer Res; 15(9); 1275-86. Ó2017 AACR.

show abstract

Medulloblastoma—Biology and Microenvironment:A Review

Cited by 10 publications

References 82 publications

Adoptive Cell Therapies for Glioblastoma

Adoptive Cell Therapies for Glioblastoma

Evidence of Tumour Microenvironment and Stromal Cellular Components in Retinoblastoma

MELK and EZH2 Cooperate to Regulate Medulloblastoma Cancer Stem-like Cell Proliferation and Differentiation

Contact Info

Product

Resources

About