Gungabeesoon, Jeremy; Gort-Freitas, Nicolas A; Kiss, Máté; Bolli, Evangelia; Messemaker, Marius; Siwicki, Marie; Hicham, Mehdi; Bill, Ruben; Koch, Peter; Cianciaruso, Chiara; Duval, Florent; Pfirschke, Christina; Mazzola, Michael; Peters, Solange; Homicsko, Krisztian; Garris, Christopher; Weissleder, Ralph; Klein, Allon M; Pittet, Mikael J (2023). A neutrophil response linked to tumor control in immunotherapy. Cell, 186(7), pp. 1448-1464. Cell Press 10.1016/j.cell.2023.02.032
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Neutrophils accumulate in solid tumors, and their abundance correlates with poor prognosis. Neutrophils are not homogeneous, however, and could play different roles in cancer therapy. Here, we investigate the role of neutrophils in immunotherapy, leading to tumor control. We show that successful therapies acutely expanded tumor neutrophil numbers. This expansion could be attributed to a Sellhi state rather than to other neutrophils that accelerate tumor progression. Therapy-elicited neutrophils acquired an interferon gene signature, also seen in human patients, and appeared essential for successful therapy, as loss of the interferon-responsive transcription factor IRF1 in neutrophils led to failure of immunotherapy. The neutrophil response depended on key components of anti-tumor immunity, including BATF3-dependent DCs, IL-12, and IFNγ. In addition, we found that a therapy-elicited systemic neutrophil response positively correlated with disease outcome in lung cancer patients. Thus, we establish a crucial role of a neutrophil state in mediating effective cancer therapy.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Clinic of Medical Oncology |
UniBE Contributor: |
Bill, Ruben |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
0092-8674 |
Publisher: |
Cell Press |
Language: |
English |
Submitter: |
Rebeka Gerber |
Date Deposited: |
18 Apr 2023 07:33 |
Last Modified: |
18 Apr 2023 07:41 |
Publisher DOI: |
10.1016/j.cell.2023.02.032 |
PubMed ID: |
37001504 |
Uncontrolled Keywords: |
IRF1 SiglecF anti-CD40 anti-PD-1 cancer immunotherapy interferon lung cancer neutrophil single-cell RNA-seq |
BORIS DOI: |
10.48350/181794 |
URI: |
https://boris.unibe.ch/id/eprint/181794 |
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