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@ARTICLE{Szlachetko:300189,
      author       = {J. A. Szlachetko and F. Hofmann-Vega and B. Budeus and
                      L.-J. Schröder and C. A. Dumitru and M. Schmidt and E.
                      Deuss and S. Vollmer and E.-M. Hanschmann and M. Busch and
                      J. Kehrmann and S. Lang and N. Dünker and T. Hussain and S.
                      Brandau$^*$},
      title        = {{T}umor cells that resist neutrophil anticancer
                      cytotoxicity acquire a prometastatic and innate immune
                      escape phenotype.},
      journal      = {Cellular $\&$ molecular immunology},
      volume       = {22},
      issn         = {1672-7681},
      address      = {London [u.a.]},
      publisher    = {Nature Publ. Group},
      reportid     = {DKFZ-2025-00666},
      pages        = {527–540},
      year         = {2025},
      note         = {volume 22, pages 527–540 (2025)},
      abstract     = {In the tumor host, neutrophils may exhibit protumor or
                      antitumor activity. It is hypothesized that in response to
                      host-derived or therapy-induced factors, neutrophils adopt
                      diverse functional states to ultimately execute these
                      differential functions. Here, we provide an alternative
                      scenario in which the response of an individual tumor cell
                      population determines the overall protumor versus antitumor
                      outcome of neutrophil‒tumor interactions. Experimentally,
                      we show that human neutrophils, which are sequentially
                      stimulated with bacteria and secreted factors from tumor
                      cells, kill a certain proportion of tumor target cells.
                      However, the majority of the tumor cells remained resistant
                      to this neutrophil-mediated killing and underwent a
                      functional, phenotypic and transcriptomic switch that was
                      reminiscent of partial epithelial‒to-mesenchymal
                      transition. This cell biological switch was associated with
                      physical escape from NK-mediated killing and resulted in
                      enhanced metastasis to the lymph nodes in a preclinical
                      orthotopic mouse model. Mechanistically, we identified the
                      antimicrobial neutrophil granule proteins neutrophil
                      elastase (NE) and matrix metalloprotease-9 (MMP-9) as the
                      molecular mediators of this functional switch. We validated
                      these data in patients with head and neck cancer and
                      identified bacterially colonized intratumoral niches that
                      were enriched for mesenchymal tumor cells and neutrophils
                      expressing NE and MMP-9. Our data reveal the parallel
                      execution of tumor cytotoxic and prometastatic activity by
                      activated neutrophils and identify NE and MMP-9 as mediators
                      of lymph node metastasis. The identified mechanism explains
                      the functional dichotomy of tumor-associated neutrophils at
                      the level of the tumor target cell response and has
                      implications for superinfected cancers and the dysbiotic
                      tumor microenvironment.},
      keywords     = {Staphylococcus aureus (Other) / Dysbiosis and oral
                      microbiome (Other) / Epithelial‒mesenchymal transition
                      (Other) / Lymphatic metastasis (Other) / Neutrophil
                      extracellular traps (Other) / Tumor-associated neutrophils
                      (Other) / neutrophil elastase (Other)},
      cin          = {ED01},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40155451},
      doi          = {10.1038/s41423-025-01283-w},
      url          = {https://inrepo02.dkfz.de/record/300189},
}