title: Type I IFNs induce anti-tumor polarization of tumor associated neutrophils in mice and human.
abstract: The importance of tumor associated neutrophils (TANs) in cancer development is in the meantime well established. Numerous of clinical data document the adverse prognostic effects of neutrophil infiltration in solid tumors. However, certain tumor therapies need functional neutrophils to be effective, suggesting altered neutrophil polarization associated with different outcomes for cancer patients. Therefore, modulation of neutrophilic phenotypes represents a potent therapeutic option, but factors mediating neutrophil polarization are still poorly defined. In this manuscript we provide evidence that type I IFNs alter neutrophilic phenotype into anti-tumor, both in mice and human. In the absence of IFN-β, pro-tumor properties, such as reduced tumor cytotoxicity with low neutrophil extracellular traps (NETs) expression, low ICAM1 and TNF-α expression, dominated neutrophil phenotypes in primary lesion and premetastatic lung. Interestingly, such neutrophils have significantly prolonged life-span. Notably, interferon therapy in mice altered TAN polarization towards anti-tumor N1. Similar changes in neutrophil activation could be observed in melanoma patients undergoing type I IFN therapy. Altogether, these data highlight the therapeutic potential of interferons, suggesting optimization of its clinical use as potent anti-tumor agent.
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection Research, HZI, Braunschweig, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Andzinski
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection Research, HZI, Braunschweig, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Kasnitz
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection Research, HZI, Braunschweig, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Stahnke
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection Research, HZI, Braunschweig, Germany.|Department of Internal Medicine, Division of Nephrology, E-DA Hospital/I-Shou University, Kaohsiung, Taiwan.
authors.forename: Ching-Fang
authors.initials: CF
authors.lastname: Wu
authors.affiliation: Immune Regulation, Helmholtz Centre for Infection Research, HZI, Braunschweig, Germany.|Infection Immunology, Institute for Medical Microbiology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Gereke
authors.affiliation: Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Hannover, Germany.
authors.forename: Maren
authors.initials: M
authors.lastname: von Köckritz-Blickwede
authors.affiliation: Department of Dermatology, University Hospital, West German Cancer Center, University Duisburg-Essen, Essen, Germany.|German Cancer Consortium (DKTK), Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Schilling
authors.affiliation: German Cancer Consortium (DKTK), Germany.|Department of Otorhinolaryngology, University Hospital, University of Duisburg-Essen, Essen, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Brandau
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection Research, HZI, Braunschweig, Germany.|Institute of Immunology, Medical School Hannover, Hannover, Germany.
authors.forename: Siegfried
authors.initials: S
authors.lastname: Weiss
authors.affiliation: Molecular Immunology, Helmholtz Centre for Infection Research, HZI, Braunschweig, Germany.|Department of Internal Medicine II, University Hospital, University of Tuebingen, Tuebingen, Germany.
authors.forename: Jadwiga
authors.initials: J
authors.lastname: Jablonska
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007370:Interferon Type I / Q000276:immunology* / Q000627:therapeutic use; D008545:Melanoma / Q000188:drug therapy / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009374:Neoplasms, Experimental / Q000276:immunology* / Q000473:pathology; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology*; D010641:Phenotype
chemical_list: D000970:Antineoplastic Agents; D007370:Interferon Type I
keywords: IFN-β; melanoma; neutrophils; polarization; tumor