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Cell Rep. 2015 Feb 3;10(4):562-73. doi: 10.1016/j.celrep.2014.12.039. Epub 2015 Jan 22.

Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer.

Author information

1
Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel Canada, Hebrew University Medical School, 91120 Jerusalem, Israel.
2
Institute of Pulmonary Medicine, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel.
3
Department of Biology, Faculty of Natural Sciences, University of Haifa, 31905 Haifa, Israel.
4
Institute of Dental Sciences, Hebrew University-Hadassah School of Dental Medicine, 91120 Jerusalem, Israel.
5
Institut for Anatomy and Cell Biology, Tumour Angiogenesis and Experimental Therapeutics, Universität Würzburg, 97070 Würzburg, Germany.
6
Institute of Pulmonary Medicine, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel. Electronic address: fridlender@hadassah.org.il.
7
Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel Canada, Hebrew University Medical School, 91120 Jerusalem, Israel. Electronic address: zvikag@ekmd.huji.ac.il.

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.

PMID:
25620698
DOI:
10.1016/j.celrep.2014.12.039
[Indexed for MEDLINE]
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