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

Research output: Contribution to journalArticlepeer-review

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 languageEnglish
Pages (from-to)562-573
Number of pages12
JournalCell Reports
Volume10
Issue number4
DOIs
StatePublished - 3 Feb 2015
Externally publishedYes

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