Cytotoxic T-lymphocytes secrete soluble factors that induce caspase-mediated apoptosis in glioblastoma cell lines

Cagigi, Alberto; Nilsson, Anna; Levitsky, Victor; Sabri, Farideh

doi:10.1016/j.jneuroim.2010.04.009

Cited by 2 publications

(1 citation statement)

References 34 publications

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“…Moreover, glioblastoma cells express the CD95 ligand [43] and may be susceptible to CD95 ligand-initiated cell killing and therapy [44]. Moreover, CD95-positive cytotoxic cells may trigger several pathways of caspase activation in glioblastoma cell lines [45]. Although the migration of activated lymphocytes between the peripheral blood and the brain has not been proven, the overall changes of immune phenotypes in GBM patients strongly suggest ongoing crosstalk between the tumor environment and the peripheral immune system (Fig.…”

Section: Discussionmentioning

confidence: 99%

Immune phenotypes predict survival in patients with glioblastoma multiforme

Mostafa

Paľa

Högel³

et al. 2016

J Hematol Oncol

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BackgroundGlioblastoma multiforme (GBM), a common primary malignant brain tumor, rarely disseminates beyond the central nervous system and has a very bad prognosis. The current study aimed at the analysis of immunological control in individual patients with GBM.MethodsImmune phenotypes and plasma biomarkers of GBM patients were determined at the time of diagnosis using flow cytometry and ELISA, respectively.ResultsUsing descriptive statistics, we found that immune anomalies were distinct in individual patients. Defined marker profiles proved highly relevant for survival. A remarkable relation between activated NK cells and improved survival in GBM patients was in contrast to increased CD39 and IL-10 in patients with a detrimental course and very short survival. Recursive partitioning analysis (RPA) and Cox proportional hazards models substantiated the relevance of absolute numbers of CD8 cells and low numbers of CD39 cells for better survival.ConclusionsDefined alterations of the immune system may guide the course of disease in patients with GBM and may be prognostically valuable for longitudinal studies or can be applied for immune intervention.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-016-0272-3) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Immune phenotypes predict survival in patients with glioblastoma multiforme

Mostafa

Paľa

Högel³

et al. 2016

J Hematol Oncol

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Involvement of the tumour necrosis factor receptor system in glioblastoma cell death induced by palbociclib-heptamethine cyanine dye conjugate

Cooper,

Oyagawa,

Johnson

et al. 2024

Cell Commun Signal

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Glioblastoma is the most common and aggressive primary brain tumour in adults. The development of anti-brain cancer agents are challenged by the blood-brain barrier and the resistance conferred by the local tumour microenvironment. Heptamethine cyanine dyes (HMCDs) are a class of near-infrared fluorescence compounds that have recently emerged as promising agents for drug delivery. We conjugated palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, to an HMCD, MHI-148, and conducted drug activity analysis on primary patient-derived glioblastoma cell lines. In addition to the expected cytostatic activity, our in vitro studies revealed that palbociclib-MHI-148 conjugate resulted in an almost 100-fold increase in cytotoxicity compared to palbociclib alone. This shift of palbociclib from cytostatic to cytotoxic when conjugated to MHI-148 was due to increased DNA damage, as indicated by an increase in γH2AX foci, followed by an increased expression of key extrinsic apoptosis genes, including TP53, TNFR1, TRAIL, FADD and caspase 8. In addition, we observed a time-dependent increase in the cell surface expression of TNFR1, consistent with an observed increase in the secretion TNFα, followed by TNFR1 endocytosis at 48 h. The treatment of patient GBM cells with the palbociclib-MHI-148 conjugate prevented TNFα-induced NFκB translocation, suggesting conjugate-induced TNFR1 signalling favoured the TNFR1-mediated apoptotic response rather than the pro-inflammatory response pathway. Notably, pharmacological inhibition of endocytosis of TNFR1, and siRNA-knockdown of TNFR1 reversed the palbociclib-MHI-148-induced cell death. These results show a novel susceptibility of glioblastoma cells to TNFR1-dependent apoptosis, dependent on inhibition of canonical NFκB signalling using our previously reported palbociclib-HMCD conjugate.

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Cytotoxic T-lymphocytes secrete soluble factors that induce caspase-mediated apoptosis in glioblastoma cell lines

Cited by 2 publications

References 34 publications

Immune phenotypes predict survival in patients with glioblastoma multiforme

Immune phenotypes predict survival in patients with glioblastoma multiforme

Involvement of the tumour necrosis factor receptor system in glioblastoma cell death induced by palbociclib-heptamethine cyanine dye conjugate

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