The failure of current immunotherapy for malignant glioma. Tumor-derived TGF-?, T-cell apoptosis, and the immune privilege of the brain

Weller, Michael; Fontana, Adriano

doi:10.1016/0165-0173(95)00010-0

Cited by 213 publications

(153 citation statements)

References 210 publications

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“…Almost all assays carried out here indicated that AhR promotes the malignant phenotype of glioma cells, as defined at the level of proliferation, clonogenicity and invasiveness, as exposure to the AhR antagonist CH-223191 or AhR gene silencing interfered with these properties (Figures 6 and 7). TGF-b has been identified as crucial factor in the malignant phenotype of glioblastomas (Weller and Fontana, 1995;Wick et al, 2001) and as a downstream target of AhR signaling (Haarmann-Stemmann et al, 2008). In non-malignant cells of AhR null mice, the LTBP-1/TGF-b pathway by AhR is regulated by diverse mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Aryl hydrocarbon receptor inhibition downregulates the TGF-β/Smad pathway in human glioblastoma cells

Pantazis²,

et al. 2009

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Section: Discussionmentioning

confidence: 99%

Aryl hydrocarbon receptor inhibition downregulates the TGF-β/Smad pathway in human glioblastoma cells

Pantazis²,

et al. 2009

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“…Tumor size was measured every second day using a metric caliper. Tumor volume is given in mm 3 . The SD observed in groups of five mice is shown.…”

Section: Protamine-stabilized Mrna As An Anti-tumor Treatmentmentioning

confidence: 99%

“…Even after surgery, radiotherapy and chemotherapy, affected patients have only a median survival expectancy of less than 12 months [2]. Although they express a variety of antigens, glioblastomas do not appear to be recognized by the immune system [3]. A reason for this apparent immune ignorance could be that glioma cells induce active immunosuppression through the release of TGF-b [4,5].…”

Section: Introductionmentioning

confidence: 99%

Therapeutic anti‐tumor immunity triggered by injections of immunostimulating single‐stranded RNA

et al. 2006

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Stabilized synthetic RNA oligonucleotides (ORN) and protected messenger RNA (mRNA) were recently discovered to possess an immunostimulatory capacity through their recognition by TLR 7 and 8. We wanted to find out whether this danger signal is capable of triggering anti-tumor immunity when injected locally into an established tumor. Using the mouse glioma tumor cell line SMA-560 in syngenic VM/Dk mice, we were able to show that intra-tumor injections of protamine-stabilized mRNA do indeed induce tumor regression and long-term anti-tumor immunity. Residual RNA-injected tumors show CD8 infiltration. Distant injections of protamine-protected mRNA and intra-tumor injection of naked mRNA also result in anti-tumor immunity. Although they are strong danger signals, RNA are labile molecules with a short half-life: they do not trigger side effects such as long-term, uncontrolled immunostimulation evidenced by splenomegaly in CpG DNA-treated mice. In conclusion, RNA molecules are potent and safe danger signals that are relevant for active immunotherapy strategies aimed at the eradication of solid tumors.

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“…Glioblastoma (GB) is the most common intrinsic malignant brain tumor with a high aggressive and a strong infiltration growth. Excessive proliferation, diffuse infiltration of surrounding brain tissue, and suppression of antitumor immune surveillance contribute to the malignant phenotype of gliomas (Weller and Fontana, 1995). Silencing of TGF-b expression by small interfering RNA (siRNA) technology has been reported to abrogate glioma cell tumorigenicity in vivo (Friese et al, 2004).…”

Section: Tgf-b and Neural Stem Cells (Nscs)mentioning

confidence: 99%

TGF-β, Neuronal Stem Cells and Glioblastoma

Golestaneh

Mishra

2005

Oncogene

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Transforming growth factor beta (TGF-b) signaling leads to a number of biological end points involving cell growth, differentiation, and morphogenesis. Typically, the cellular effect accompanies an induction of mesodermal cell fate and inhibition of neural cell differentiation. However, during pathological conditions, these defined effects of TGF-b can be reversed; for example, the growthinhibitory effect is replaced with its tumor promoting ability. A multitude of factors and cross-signaling pathways have been reported to be involved in modulating the dual effects of TGF-b. In this review, we focus on the potential role of TGF-b signal transduction during development of neural progenitor cells and its relation to glioblastoma development from neural stem cells.

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The failure of current immunotherapy for malignant glioma. Tumor-derived TGF-?, T-cell apoptosis, and the immune privilege of the brain

Cited by 213 publications

References 210 publications

Aryl hydrocarbon receptor inhibition downregulates the TGF-β/Smad pathway in human glioblastoma cells

Aryl hydrocarbon receptor inhibition downregulates the TGF-β/Smad pathway in human glioblastoma cells

Therapeutic anti‐tumor immunity triggered by injections of immunostimulating single‐stranded RNA

TGF-β, Neuronal Stem Cells and Glioblastoma

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