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.
Bibliographical noteFunding Information:
Z.G. is supported by grants from the I-CORE Gene Regulation in Complex Human Disease, Center no. 41/11, the Abisch-Frenkel Foundation, the Rosetrees Trust, the Israel Cancer Research Foundation (RCDA grant), and the CONCERN foundation. Z.G.F. is supported by grants from the Israel Cancer Research Foundation (RCDA grant), Chief Scientist of the Israel Ministry of Health, and the Israel Lung Association. We thank Dr. Myriam Grunewald for critical reading of this manuscript. D.L. is supported by the Azrieli Foundation Fellowship for which she is grateful.
© 2015 The Authors.