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Updated: Sep 5, 2025

Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
Interferon-γ resistance and immune evasion in glioma develop via Notch-regulated co-evolution of malignant and immune
Elena Parmigiani1, Robert Ivanek2, Chiara Rolando1
1Embryology and Stem Cell Biology, Department of Biomedicine, University of Basel, Mattenstrasse 28, 4058 Basel, Switzerland.
Abstract:
Immune surveillance is critical to prevent tumorigenesis. Gliomas evade immune attack, but the underlying mechanisms remain poorly understood. We show that glioma cells can sustain growth independent of immune system constraint by reducing Notch signaling. Loss of Notch activity in a mouse model of glioma impairs MHC-I and cytokine expression and curtails the recruitment of anti-tumor immune cell populations in favor of immunosuppressive tumor-associated microglia/macrophages (TAMs). Depletion of T cells simulates Notch inhibition and facilitates tumor initiation. Furthermore, Notch-depleted glioma cells acquire resistance to interferon-γ and TAMs re-educating therapy. Decreased interferon response and cytokine expression by human and mouse glioma cells correlate with low Notch activity. These effects are paralleled by upregulation of oncogenes and downregulation of quiescence genes. Hence, suppression of Notch signaling enables gliomas to evade immune surveillance and increases aggressiveness. Our findings provide insights into how brain tumor cells shape their microenvironment to evade immune niche control.
Insights
Glioma cells reduce Notch signaling to evade immune surveillance, promoting tumor growth. Suppressing Notch impairs anti-tumor immunity and increases glioma aggressiveness.
Area of Science:
- Neuro-oncology
- Immunology
- Cellular signaling
Background:
- Immune surveillance is crucial for preventing cancer, but gliomas effectively evade immune attack.
- The mechanisms by which gliomas escape immune detection are not fully understood.
Purpose of the Study:
- To investigate the role of Notch signaling in glioma immune evasion.
- To elucidate how glioma cells modulate their microenvironment to resist immune surveillance.
Main Methods:
- Utilized a mouse model of glioma to study the effects of Notch signaling.
- Analyzed changes in MHC-I, cytokine expression, and immune cell populations.
- Investigated the impact of Notch depletion on glioma cell resistance to therapies.
Main Results:
- Reduced Notch signaling in glioma cells impairs MHC-I and cytokine expression.
- Loss of Notch activity promotes immunosuppressive tumor-associated microglia/macrophages (TAMs) and reduces anti-tumor T cells.
- Notch-depleted gliomas exhibit resistance to interferon-γ and TAMs re-educating therapy.
- Low Notch activity correlates with increased oncogene expression and decreased quiescence genes.
Conclusions:
- Suppression of Notch signaling is a key mechanism for gliomas to evade immune surveillance.
- Downregulation of Notch signaling enhances glioma aggressiveness and resistance to immune-mediated control.
- Targeting Notch signaling could offer new therapeutic strategies for glioma treatment.
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