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

2.50
Hdl Handle:
http://hdl.handle.net/10033/619954
Title:
Type I IFNs induce anti-tumor polarization of tumor associated neutrophils in mice and human.
Authors:
Andzinski, Lisa; Kasnitz, Nadine; Stahnke, Stephanie; Wu, Ching-Fang; Gereke, Marcus; von Köckritz-Blickwede, Maren; Schilling, Bastian; Brandau, Sven; Weiss, Siegfried; Jablonska, Jadwiga
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.
Affiliation:
Helmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Citation:
Type I IFNs induce anti-tumor polarization of tumor associated neutrophils in mice and human. 2016, 138 (8):1982-93 Int. J. Cancer
Journal:
International journal of cancer
Issue Date:
15-Apr-2016
URI:
http://hdl.handle.net/10033/619954
DOI:
10.1002/ijc.29945
PubMed ID:
26619320
Type:
Article
Language:
en
ISSN:
1097-0215
Appears in Collections:
publications of the research group molecular Immunology (MOLI)

Full metadata record

DC FieldValue Language
dc.contributor.authorAndzinski, Lisaen
dc.contributor.authorKasnitz, Nadineen
dc.contributor.authorStahnke, Stephanieen
dc.contributor.authorWu, Ching-Fangen
dc.contributor.authorGereke, Marcusen
dc.contributor.authorvon Köckritz-Blickwede, Marenen
dc.contributor.authorSchilling, Bastianen
dc.contributor.authorBrandau, Svenen
dc.contributor.authorWeiss, Siegfrieden
dc.contributor.authorJablonska, Jadwigaen
dc.date.accessioned2016-09-07T08:42:26Z-
dc.date.available2016-09-07T08:42:26Z-
dc.date.issued2016-04-15-
dc.identifier.citationType I IFNs induce anti-tumor polarization of tumor associated neutrophils in mice and human. 2016, 138 (8):1982-93 Int. J. Canceren
dc.identifier.issn1097-0215-
dc.identifier.pmid26619320-
dc.identifier.doi10.1002/ijc.29945-
dc.identifier.urihttp://hdl.handle.net/10033/619954-
dc.description.abstractThe 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.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subject.meshAnimalsen
dc.subject.meshAntineoplastic Agentsen
dc.subject.meshCell Line, Tumoren
dc.subject.meshCell Separationen
dc.subject.meshFemaleen
dc.subject.meshFlow Cytometryen
dc.subject.meshHumansen
dc.subject.meshInterferon Type Ien
dc.subject.meshMelanomaen
dc.subject.meshMiceen
dc.subject.meshMice, Inbred BALB Cen
dc.subject.meshMice, Knockouten
dc.subject.meshNeoplasms, Experimentalen
dc.subject.meshNeutrophil Infiltrationen
dc.subject.meshNeutrophilsen
dc.subject.meshPhenotypeen
dc.titleType I IFNs induce anti-tumor polarization of tumor associated neutrophils in mice and human.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.en
dc.identifier.journalInternational journal of canceren

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