Bcl-xL blockade targets neutrophils and synergizes with chemotherapy in lung squamous cell carcinoma
mouse model, where we demonstrate increased TAN survival with a rise in Bcl-xL similarly to LUAD. However, unlike in LUAD, inhibiting Bcl-xL alone was insufficient to alter tumor progression in LUSC. After carboplatin and paclitaxel treatment, a combination chemotherapy used in human LUSC, we detected increased neutrophils in circulation, spleen and tumors, and increased Bcl-xL in neutrophils and TANs. Bcl-xL blockade decreased the pool of Bcl-xL-high TANs and synergized with chemotherapy. Altogether, our results suggest distinct outcomes for targeting TANs in different tumor types and reinforce the concept of repurposing BH3 mimetics against cancer.
Authors
- Thierry Berghmans (ORCID: https://orcid.org/0000-0001-7447-2519)
- Fabienne Andris (ORCID: https://orcid.org/0000-0002-8644-1020)
- Etienne Meylan (ORCID: https://orcid.org/0000-0002-0899-2230)
- Abbie S. Ireland (ORCID: https://orcid.org/0000-0002-4178-7239)
- Sarika Rana (ORCID: https://orcid.org/0000-0002-8905-0113)
- Beatrice Parma (ORCID: https://orcid.org/0009-0001-8335-3121)
- Sébastien Denanglaire (ORCID: https://orcid.org/0000-0001-7985-716X)
- Déborah Lécuyer
- Stanislas Goriely (ORCID: https://orcid.org/0000-0002-7005-6195)
- Trudy G. Oliver (ORCID: https://orcid.org/0000-0003-2082-2397)
- Anita Bodac (ORCID: https://orcid.org/0000-0001-6118-7946)
- Jean Yannis Perentes (ORCID: https://orcid.org/0000-0001-7918-0793)
- Pieter Demetter (ORCID: https://orcid.org/0000-0001-7981-4645)
- Abdullah Mayet
- Amaury Defruit
- Mariana Brandão
Institutions
- Université Libre de Bruxelles (BE)
- Duke University (US)
- Institut Jules Bordet (BE)
- Centre Hospitalier Universitaire Vaudois (CH)
- Institute of Pathology and Genetics (BE)
- Swiss Cancer Center Léman (CH)
- École Polytechnique Fédérale de Lausanne (CH)
- University of Lausanne (CH)
Publication Details
- Journal
- EMBO Molecular Medicine
- Published
- 2026-03-31
- DOI
- https://doi.org/10.1038/s44321-026-00401-z
- Primary Topic
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Fonds De La Recherche Scientifique - FNRS
- Fondation Rose et Jean Hoguet