Cell Reports
Volume 10, Issue 4, 3 February 2015, Pages 562-573
Journal home page for Cell Reports

Article
Phenotypic Diversity and Plasticity in Circulating Neutrophil Subpopulations in Cancer

https://doi.org/10.1016/j.celrep.2014.12.039Get rights and content
Under a Creative Commons license
open access

Highlights

  • Low-density neutrophils are preferentially propagated in cancer

  • LDNs consist of both mature and immature neutrophils

  • The mature subtype of LDNs acquires suppressive functions

  • Neutrophil contribution switches from anti- to protumor with tumor progression

Summary

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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This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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Co-senior author