Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2041444 | Cell Reports | 2015 | 12 Pages |
•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
SummaryControversy 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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