Journal
CELL REPORTS
Volume 10, Issue 4, Pages 562-573Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2014.12.039
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Funding
- I-CORE Gene Regulation in Complex Human Disease [41/11]
- Abisch-Frenkel Foundation
- Rosetrees Trust
- Israel Cancer Research Foundation (RCDA grant)
- CONCERN foundation
- Chief Scientist of the Israel Ministry of Health
- Israel Lung Association
- Azrieli Foundation Fellowship
- Rosetrees Trust [M339] Funding Source: researchfish
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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-beta-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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