title: Phenotypic diversity and plasticity in circulating neutrophil subpopulations in cancer.
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.
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel Canada, Hebrew University Medical School, 91120 Jerusalem, Israel.
authors.forename: Jitka Y
authors.initials: JY
authors.lastname: Sagiv
authors.affiliation: Institute of Pulmonary Medicine, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel.
authors.forename: Janna
authors.initials: J
authors.lastname: Michaeli
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel Canada, Hebrew University Medical School, 91120 Jerusalem, Israel.
authors.forename: Simaan
authors.initials: S
authors.lastname: Assi
authors.affiliation: Institute of Pulmonary Medicine, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel.
authors.forename: Inbal
authors.initials: I
authors.lastname: Mishalian
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel Canada, Hebrew University Medical School, 91120 Jerusalem, Israel.
authors.forename: Hen
authors.initials: H
authors.lastname: Kisos
authors.affiliation: Institute of Pulmonary Medicine, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel.
authors.forename: Liran
authors.initials: L
authors.lastname: Levy
authors.affiliation: Institute of Pulmonary Medicine, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel.
authors.forename: Pazzit
authors.initials: P
authors.lastname: Damti
authors.affiliation: Department of Biology, Faculty of Natural Sciences, University of Haifa, 31905 Haifa, Israel.
authors.forename: Delphine
authors.initials: D
authors.lastname: Lumbroso
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel Canada, Hebrew University Medical School, 91120 Jerusalem, Israel.
authors.forename: Lola
authors.initials: L
authors.lastname: Polyansky
authors.affiliation: Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel Canada, Hebrew University Medical School, 91120 Jerusalem, Israel.
authors.forename: Ronit V
authors.initials: RV
authors.lastname: Sionov
authors.affiliation: Department of Biology, Faculty of Natural Sciences, University of Haifa, 31905 Haifa, Israel.
authors.forename: Amiram
authors.initials: A
authors.lastname: Ariel
authors.affiliation: Institute of Dental Sciences, Hebrew University-Hadassah School of Dental Medicine, 91120 Jerusalem, Israel.
authors.forename: Avi-Hai
authors.initials: AH
authors.lastname: Hovav
authors.affiliation: Institut for Anatomy and Cell Biology, Tumour Angiogenesis and Experimental Therapeutics, Universität Würzburg, 97070 Würzburg, Germany.
authors.forename: Erik
authors.initials: E
authors.lastname: Henke
authors.affiliation: Institute of Pulmonary Medicine, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel. Electronic address: fridlender@hadassah.org.il.
authors.forename: Zvi G
authors.initials: ZG
authors.lastname: Fridlender
authors.affiliation: 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.
authors.forename: Zvi
authors.initials: Z
authors.lastname: Granot
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000276:immunology / Q000473:pathology*; D009504:Neutrophils / Q000166:cytology*