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Int J Cancer. 2016 Apr 15;138(8):1982-93. doi: 10.1002/ijc.29945. Epub 2015 Dec 17.

Type I IFNs induce anti-tumor polarization of tumor associated neutrophils in mice and human.

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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.
Immune Regulation, Helmholtz Centre for Infection Research, HZI, Braunschweig, Germany.
Infection Immunology, Institute for Medical Microbiology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Hannover, Germany.
Department of Dermatology, University Hospital, West German Cancer Center, University Duisburg-Essen, Essen, Germany.
German Cancer Consortium (DKTK), Germany.
Department of Otorhinolaryngology, University Hospital, University of Duisburg-Essen, Essen, Germany.
Institute of Immunology, Medical School Hannover, Hannover, Germany.
Department of Internal Medicine II, University Hospital, University of Tuebingen, Tuebingen, Germany.


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.


IFN-β; melanoma; neutrophils; polarization; tumor

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