Parmigiani, Elena; Ivanek, Robert; Rolando, Chiara; Hafen, Katrin; Turchinovich, Gleb; Lehmann, Frank Michael; Gerber, Alexandra; Brkic, Sime; Frank, Stephan; Meyer, Sara C; Wakimoto, Hiroaki; Günel, Murat; Louvi, Angeliki; Mariani, Luigi; Finke, Daniela; Holländer, Georg; Hutter, Gregor; Tussiwand, Roxane; Taylor, Verdon and Giachino, Claudio (2022). Interferon-γ resistance and immune evasion in glioma develop via Notch-regulated co-evolution of malignant and immune cells. Developmental cell, 57(15), 1847-1865.e9. Elsevier 10.1016/j.devcel.2022.06.006
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Haematology and Central Haematological Laboratory |
UniBE Contributor: |
Meyer, Sara Christina |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1878-1551 |
Publisher: |
Elsevier |
Language: |
English |
Submitter: |
Pierrette Durand Lüthi |
Date Deposited: |
02 Dec 2022 16:08 |
Last Modified: |
05 Dec 2022 16:29 |
Publisher DOI: |
10.1016/j.devcel.2022.06.006 |
PubMed ID: |
35803280 |
Uncontrolled Keywords: |
MHC MYC T cells cytokines immune evasion interferon-γ niche tumor microenvironment tumor suppressor tumor-associated microglia/macrophages |
BORIS DOI: |
10.48350/175439 |
URI: |
https://boris.unibe.ch/id/eprint/175439 |
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