HLA-E contributes to an immune-inhibitory phenotype of glioblastoma stem-like cells

Wolpert, Fabian; Roth, Patrick; Lamszus, Katrin; Tabatabai, Ghazaleh; Weller, Michael; Eisele, Günter

doi:10.1016/j.jneuroim.2012.05.010

Cited by 38 publications

(34 citation statements)

References 43 publications

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“…In contrast, several recent studies have demonstrated that a murine xenograft model using human BCSCs has the ability to recapitulate human GBM histopathology (37,56). To test whether BCSCs were able to form such tumors in nude rats, we inoculated GS5, a well-characterized BCSC line (37,57) in rat brains. Consistent with the findings in mouse brains (37,57), GS5 tumors in the brain of nude rats are highly infiltrative and histopathologically similar to human GBM (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Highly penetrative, drug-loaded nanocarriers improve treatment of glioblastoma

Zhou

Patel

Sirianni³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

226

227

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Current therapy for glioblastoma multiforme is insufficient, with nearly universal recurrence. Available drug therapies are unsuccessful because they fail to penetrate through the region of the brain containing tumor cells and they fail to kill the cells most responsible for tumor development and therapy resistance, brain cancer stem cells (BCSCs). To address these challenges, we combined two major advances in technology: ( i ) brain-penetrating polymeric nanoparticles that can be loaded with drugs and are optimized for intracranial convection-enhanced delivery and ( ii ) repurposed compounds, previously used in Food and Drug Administration-approved products, which were identified through library screening to target BCSCs. Using fluorescence imaging and positron emission tomography, we demonstrate that brain-penetrating nanoparticles can be delivered to large intracranial volumes in both rats and pigs. We identified several agents (from Food and Drug Administration-approved products) that potently inhibit proliferation and self-renewal of BCSCs. When loaded into brain-penetrating nanoparticles and administered by convection-enhanced delivery, one of these agents, dithiazanine iodide, significantly increased survival in rats bearing BCSC-derived xenografts. This unique approach to controlled delivery in the brain should have a significant impact on treatment of glioblastoma multiforme and suggests previously undescribed routes for drug and gene delivery to treat other diseases of the central nervous system.

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Section: Resultsmentioning

confidence: 99%

“…To test whether BCSCs were able to form such tumors in nude rats, we inoculated GS5, a well-characterized BCSC line (37,57) in rat brains. Consistent with the findings in mouse brains (37,57), GS5 tumors in the brain of nude rats are highly infiltrative and histopathologically similar to human GBM (Fig. S2 B and C).…”

Section: Resultsmentioning

confidence: 99%

Highly penetrative, drug-loaded nanocarriers improve treatment of glioblastoma

Zhou

Patel

Sirianni³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

226

227

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“…HLA-E gene silencing in glioma CSCs can enhance the susceptibility to NK-cell mediated lysis [207]. Similarly, the CD44 hi CD24 lo population has also been found to be more immunoresistant in other breast cancer cell lines, such as SK-BR3, MDA-MB-231, and BT474 cells.…”

Section: Csc Immunoselection With Natural Killer Cellsmentioning

confidence: 95%

Strategies for Isolating and Enriching Cancer Stem Cells: Well Begun Is Half Done

Duan

Qiu

et al. 2013

Stem Cells and Development

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Cancer stem cells (CSCs) constitute a subpopulation of cancer cells that have the potential for self-renewal, multipotent differentiation, and tumorigenicity. Studies on CSC biology and CSC-targeted therapies depend on CSC isolation and/or enrichment methodologies. Scientists have conducted extensive research in this field since John Dick's group successfully isolated CSCs based on the expression of the CD34 and CD38 surface markers. Progress in CSC research has been greatly facilitated by the enrichment and isolation of these cells. In this review, we summarize the current strategies used in our and other laboratories for CSC isolation and enrichment, including methods based on stem cell surface markers, intracellular enzyme activity, the concentration of reactive oxygen species, the mitochondrial membrane potential, promoter-driven fluorescent protein expression, autofluorescence, suspension/adherent culture, cell division, the identification of side population cells, resistance to cytotoxic compounds or hypoxia, invasiveness/adhesion, immunoselection, and physical property. Although many challenges remain to be overcome, it is reasonable to believe that more reliable, efficient, and convenient methods will be developed in the near future.

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“…Subsequent studies confirmed and extended these findings by showing HLA-E expression to be associated with a subset of glioma cells with tumor-initiating properties. 33 HLA-E inhibited recognition and killing of these glioma-initiating cells by NK cells, interfering with HLA-E expression by siRNA-gene silencing restored NK killing.…”

Section: Natural Killer Cellsmentioning

confidence: 96%

CD8+ T Cell-Independent Immune-Mediated Mechanisms of Anti-Tumor Activity

2015

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Despite the growing number of preclinical and clinical trials focused on immunotherapy for the treatment of malignant gliomas, the prognosis for this disease remains grim. Cancer immunotherapy seeks to recruit an effective immune response to eliminate tumor cells. To date, cancer vaccines have shown only limited effectiveness because of our incomplete understanding of the necessary effector cells and mechanisms that yield efficient tumor clearance. CD8+ T cell cytotoxic activity has long been proposed as the primary effector function necessary for tumor regression. However, there is increasing evidence that indicates that components of the immune system other than CD8+ T cells play important roles in tumor eradication and control. The following review should provide an understanding of the mechanisms involved in an effective antitumor response to guide future therapeutic designs. The information provided suggests an alternate means of effective tumor clearance in malignant glioma to the canonical CD8+ cytotoxic T cell mechanism.

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HLA-E contributes to an immune-inhibitory phenotype of glioblastoma stem-like cells

Cited by 38 publications

References 43 publications

Highly penetrative, drug-loaded nanocarriers improve treatment of glioblastoma

Highly penetrative, drug-loaded nanocarriers improve treatment of glioblastoma

Strategies for Isolating and Enriching Cancer Stem Cells: Well Begun Is Half Done

CD8+ T Cell-Independent Immune-Mediated Mechanisms of Anti-Tumor Activity

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