2. Academic Validation
  3. G-CSF/NAMPT signaling drives neutrophil dysfunction and enhances bacterial infection susceptibility in cancer patients

G-CSF/NAMPT signaling drives neutrophil dysfunction and enhances bacterial infection susceptibility in cancer patients

  • Nat Commun. 2025 Dec 12;16(1):11137. doi: 10.1038/s41467-025-67471-4.
Ekaterina Pylaeva 1 2,  Lea Tollrian 1,  Jana Riedesel 1,  Olga Shevchuk 3,  Ilona Thiel 1,  Irem Ozel 1,  Nastassia Kabankova 1,  Hannah Voß 3,  Bente Siebels 4,  Hartmut Schlüter 4,  Corinna Haist 5,  Helmut Hanenberg 5 6,  Stefan Mattheis 1,  Cornelius Kürten 1,  Markus Sperandio 7,  Jan Kehrmann 8,  Daniel Robert Engel 3,  Stephan Lang 1 2,  Jadwiga Jablonska 9 10
Affiliations

Affiliations

  • 1 Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
  • 2 German Cancer Consortium (DKTK) partner site Düsseldorf/Essen, Essen, Germany.
  • 3 Department of Immunodynamics, Institute for Experimental Immunology and Imaging, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
  • 4 Section Mass Spectrometry and Proteomics, Center for Diagnostics, University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany.
  • 5 Department of Otorhinolaryngology and Head/Neck Surgery, Heinrich Heine University, Düsseldorf, Germany.
  • 6 Department of Pediatrics III, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
  • 7 Institute of Cardiovascular Physiology and Pathophysiology, Biomedical Center, Ludwig Maximilian University of Munich, Munich, Germany.
  • 8 Institute of Medical Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
  • 9 Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. [email protected].
  • 10 German Cancer Consortium (DKTK) partner site Düsseldorf/Essen, Essen, Germany. [email protected].
PMID: 41387444 DOI: 10.1038/s41467-025-67471-4
Abstract

Despite advancements in Cancer therapies, Bacterial complications remain a major challenge, delaying treatment and worsening outcomes. While immunosuppressive therapies and prolonged hospitalizations contribute, they do not fully explain the elevated Infection risk in Cancer patients. Here we show that tumors producing high levels of granulocyte colony-stimulating factor (G-CSF) promote the persistence of Gram-negative pathogens in head and neck squamous cell carcinoma due to neutrophil reprogramming. Mechanistically, we identify tumor-driven activation of the G-CSF / nicotinamide phosphoribosyltransferase (NAMPT) signaling axis in neutrophil progenitors, resulting in impaired Antibacterial functions, such as phagocytosis and neutrophil extracellular traps formation, and development of tissue-damaging neutrophil subsets. This disrupts lung tissue integrity and facilitates Bacterial persistence. Importantly, targeting the G-CSF/NAMPT pathway prevents the generation of dysfunctional neutrophils and improves Bacterial clearance in vivo. Our findings reveal tumor-induced, NAMPT-dependent neutrophil reprogramming as a central driver of compromised antimicrobial defenses in Cancer. Therapeutic strategies aimed at modulating G-CSF/NAMPT signaling could enhance Infection control and survival for Cancer patients.

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