Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer

Jitka Y. Sagiv; Janna Michaeli; Simaan Assi; Inbal Mishalian; Hen Kisos; Liran Levy; Pazzit Damti; Delphine Lumbroso; Lola Polyansky; Ronit V. Sionov; Amiram Ariel; Avi Hai Hovav; Erik Henke; Zvi G. Fridlender; Zvi Granot

doi:10.1016/j.celrep.2014.12.039

Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer

Jitka Y. Sagiv, Janna Michaeli, Simaan Assi, Inbal Mishalian, Hen Kisos, Liran Levy, Pazzit Damti, Delphine Lumbroso, Lola Polyansky, Ronit V. Sionov, Amiram Ariel, Avi Hai Hovav, Erik Henke, Zvi G. Fridlender^*, Zvi Granot

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

520 Scopus citations

Abstract

Controversy surrounds neutrophil function in cancer because neutrophils were shown to provide both pro- and antitumor functions. We identified a heterogeneous subset of low-density neutrophils (LDNs) that appear transiently in self-resolving inflammation but accumulate continuously with cancer progression. LDNs display impaired neutrophil function and immunosuppressive properties, characteristics that are in stark contrast to those of mature, high-density neutrophils (HDNs). LDNs consist of both immature myeloid-derived suppressor cells (MDSCs) and mature cells that are derived from HDNs in a TGF-β-dependent mechanism. Our findings identify three distinct populations of circulating neutrophils and challenge the concept that mature neutrophils have limited plasticity. Furthermore, our findings provide a mechanistic explanation to mitigate the controversy surrounding neutrophil function in cancer.

Original language	American English
Pages (from-to)	562-573
Number of pages	12
Journal	Cell Reports
Volume	10
Issue number	4
DOIs	https://doi.org/10.1016/j.celrep.2014.12.039
State	Published - 3 Feb 2015

Bibliographical note

Funding Information:
Z.G. is supported by grants from the I-CORE Gene Regulation in Complex Human Disease, Center no. 41/11, the Abisch-Frenkel Foundation, the Rosetrees Trust, the Israel Cancer Research Foundation (RCDA grant), and the CONCERN foundation. Z.G.F. is supported by grants from the Israel Cancer Research Foundation (RCDA grant), Chief Scientist of the Israel Ministry of Health, and the Israel Lung Association. We thank Dr. Myriam Grunewald for critical reading of this manuscript. D.L. is supported by the Azrieli Foundation Fellowship for which she is grateful.

Publisher Copyright:
© 2015 The Authors.

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10.1016/j.celrep.2014.12.039

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title = "Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer",

abstract = "Controversy surrounds neutrophil function in cancer because neutrophils were shown to provide both pro- and antitumor functions. We identified a heterogeneous subset of low-density neutrophils (LDNs) that appear transiently in self-resolving inflammation but accumulate continuously with cancer progression. LDNs display impaired neutrophil function and immunosuppressive properties, characteristics that are in stark contrast to those of mature, high-density neutrophils (HDNs). LDNs consist of both immature myeloid-derived suppressor cells (MDSCs) and mature cells that are derived from HDNs in a TGF-β-dependent mechanism. Our findings identify three distinct populations of circulating neutrophils and challenge the concept that mature neutrophils have limited plasticity. Furthermore, our findings provide a mechanistic explanation to mitigate the controversy surrounding neutrophil function in cancer.",

author = "Sagiv, {Jitka Y.} and Janna Michaeli and Simaan Assi and Inbal Mishalian and Hen Kisos and Liran Levy and Pazzit Damti and Delphine Lumbroso and Lola Polyansky and Sionov, {Ronit V.} and Amiram Ariel and Hovav, {Avi Hai} and Erik Henke and Fridlender, {Zvi G.} and Zvi Granot",

note = "Funding Information: Z.G. is supported by grants from the I-CORE Gene Regulation in Complex Human Disease, Center no. 41/11, the Abisch-Frenkel Foundation, the Rosetrees Trust, the Israel Cancer Research Foundation (RCDA grant), and the CONCERN foundation. Z.G.F. is supported by grants from the Israel Cancer Research Foundation (RCDA grant), Chief Scientist of the Israel Ministry of Health, and the Israel Lung Association. We thank Dr. Myriam Grunewald for critical reading of this manuscript. D.L. is supported by the Azrieli Foundation Fellowship for which she is grateful. Publisher Copyright: {\textcopyright} 2015 The Authors.",

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AU - Levy, Liran

AU - Damti, Pazzit

AU - Lumbroso, Delphine

AU - Polyansky, Lola

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AU - Ariel, Amiram

AU - Hovav, Avi Hai

AU - Henke, Erik

AU - Fridlender, Zvi G.

AU - Granot, Zvi

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N2 - Controversy surrounds neutrophil function in cancer because neutrophils were shown to provide both pro- and antitumor functions. We identified a heterogeneous subset of low-density neutrophils (LDNs) that appear transiently in self-resolving inflammation but accumulate continuously with cancer progression. LDNs display impaired neutrophil function and immunosuppressive properties, characteristics that are in stark contrast to those of mature, high-density neutrophils (HDNs). LDNs consist of both immature myeloid-derived suppressor cells (MDSCs) and mature cells that are derived from HDNs in a TGF-β-dependent mechanism. Our findings identify three distinct populations of circulating neutrophils and challenge the concept that mature neutrophils have limited plasticity. Furthermore, our findings provide a mechanistic explanation to mitigate the controversy surrounding neutrophil function in cancer.

AB - Controversy surrounds neutrophil function in cancer because neutrophils were shown to provide both pro- and antitumor functions. We identified a heterogeneous subset of low-density neutrophils (LDNs) that appear transiently in self-resolving inflammation but accumulate continuously with cancer progression. LDNs display impaired neutrophil function and immunosuppressive properties, characteristics that are in stark contrast to those of mature, high-density neutrophils (HDNs). LDNs consist of both immature myeloid-derived suppressor cells (MDSCs) and mature cells that are derived from HDNs in a TGF-β-dependent mechanism. Our findings identify three distinct populations of circulating neutrophils and challenge the concept that mature neutrophils have limited plasticity. Furthermore, our findings provide a mechanistic explanation to mitigate the controversy surrounding neutrophil function in cancer.

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Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer

Abstract

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