title: Transcriptomic analysis comparing tumor-associated neutrophils with granulocytic myeloid-derived suppressor cells and normal neutrophils.
abstract: The role of myeloid cells in supporting cancer growth is well established. Most work has focused on myeloid-derived suppressor cells (MDSC) that accumulate in tumor-bearing animals, but tumor-associated neutrophils (TAN) are also known to be capable of augmenting tumor growth. However, little is known about their evolution, phenotype, and relationship to naïve neutrophils (NN) and to the granulocytic fraction of MDSC (G-MDSC).In the current study, a transcriptomics approach was used in mice to compare these cell types. Our data show that the three populations of neutrophils are significantly different in their mRNA profiles with NN and G-MDSC being more closely related to each other than to TAN. Structural genes and genes related to cell-cytotoxicity (i.e. respiratory burst) were significantly down-regulated in TAN. In contrast, many immune-related genes and pathways, including genes related to the antigen presenting complex (e.g. all six MHC-II complex genes), and cytokines (e.g. TNF-α, IL-1-α/β), were up-regulated in G-MDSC, and further up-regulated in TAN. Thirteen of the 25 chemokines tested were markedly up-regulated in TAN compared to NN, including striking up-regulation of chemoattractants for T/B-cells, neutrophils and macrophages.This study characterizes different populations of neutrophils related to cancer, pointing out the major differences between TAN and the other neutrophil populations.
authors.affiliation: Institute of Pulmonary Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. fridlender@hadassah.org.il
authors.forename: Zvi G
authors.initials: ZG
authors.lastname: Fridlender
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Inbal
authors.initials: I
authors.lastname: Mishalian
authors.forename: Sunil
authors.initials: S
authors.lastname: Singhal
authors.forename: Guanjun
authors.initials: G
authors.lastname: Cheng
authors.forename: Veena
authors.initials: V
authors.lastname: Kapoor
authors.forename: Wenhwai
authors.initials: W
authors.lastname: Horng
authors.forename: Gil
authors.initials: G
authors.lastname: Fridlender
authors.forename: Rachel
authors.initials: R
authors.lastname: Bayuh
authors.forename: G Scott
authors.initials: GS
authors.lastname: Worthen
authors.forename: Steven M
authors.initials: SM
authors.lastname: Albelda
mesh_terms: D000818:Animals; D015972:Gene Expression Regulation, Neoplastic; D006098:Granulocytes / Q000473:pathology*; D007109:Immunity / Q000235:genetics; D051379:Mice; D022423:Myeloid Cells / Q000473:pathology*; D009369:Neoplasms / Q000276:immunology / Q000473:pathology*; D009504:Neutrophils / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D016897:Respiratory Burst / Q000235:genetics; D059467:Transcriptome
chemical_list: D012333:RNA, Messenger