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Published on: November 28, 2019
Tumor necrosis factor reduces brain tumor growth by enhancing macrophage recruitment and microcyst formation
Jérôme Villeneuve1, Pierrot Tremblay, Luc Vallières
1Department of Oncology and Molecular Endocrinology, Laval University Hospital Research Center, Québec City, Québec, Canada. Luc.Vallieres@crchul.ulaval.ca
Abstract:
Recent findings implicate macrophages and some of their secreted products, especially tumor necrosis factor (TNF), as tumor promoters. Inhibitors of these inflammatory components are currently regarded as potential therapeutic tools to block tumor progression. Here, we show that infiltrating macrophages represented a significant population of nonneoplastic cells within malignant gliomas, in which they were the exclusive producers of TNF. Contrary to the reported pro-oncogenic effects of TNF in other types of solid tumors, glioma-bearing mice deficient in TNF developed larger tumors and had reduced survival compared with their wild-type controls. Histologic examinations revealed that glioma volume was negatively correlated with the number of macrophages and small cavities called microcysts. Overall, our results support the concept that macrophages alter brain tumor development through a TNF-dependent process that culminates in the formation of microcysts. This raises the question of whether anti-inflammatory drugs, such as those commonly administrated to patients with brain cancer, could interfere with antitumor mechanisms.
Insights
Macrophages promote brain tumor growth by producing tumor necrosis factor (TNF), which forms microcysts. Inhibiting TNF may hinder this anti-tumor mechanism, suggesting caution with anti-inflammatory drugs in brain cancer therapy.
Area of Science:
- Neuro-oncology
- Immunology
- Cancer Biology
Background:
- Macrophages infiltrate malignant gliomas and are key producers of tumor necrosis factor (TNF).
- TNF is often implicated as a tumor promoter in various cancers.
- The role of TNF in brain tumors, specifically gliomas, requires further investigation.
Purpose of the Study:
- To investigate the role of tumor necrosis factor (TNF)-producing macrophages in glioma development.
- To determine the impact of TNF deficiency on glioma progression and survival in a mouse model.
- To explore the relationship between macrophage infiltration, microcyst formation, and glioma volume.
Main Methods:
- Utilized genetically modified mice deficient in TNF.
- Conducted histological examinations of gliomas in both TNF-deficient and wild-type mice.
- Quantified macrophage infiltration and microcyst formation within tumors.
Main Results:
- Mice lacking TNF developed larger gliomas and exhibited reduced survival compared to controls.
- A negative correlation was observed between glioma volume and the number of infiltrating macrophages and microcysts.
- Macrophages were identified as the exclusive source of TNF within malignant gliomas.
Conclusions:
- Tumor necrosis factor (TNF) produced by tumor-associated macrophages plays a protective role in glioma development.
- Macrophage-derived TNF promotes the formation of microcysts, which are associated with reduced tumor growth.
- The findings suggest that anti-inflammatory drugs targeting TNF could potentially interfere with endogenous anti-tumor mechanisms in brain cancer.
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