title: Priming of neutrophils toward NETosis promotes tumor growth.
abstract: Neutrophils play a major role in cancer biology and both pro- and antitumoral functions of tumor-infiltrating neutrophils have been described. We have shown that tumors, by releasing G-CSF into the bloodstream, prime circulating neutrophils to form neutrophil extracellular traps (NETs) and we have detected the presence of NETs within the tumor microenvironment. Here, we report, using PAD4-deficient mice with a defect in neutrophil chromatin decondensation and NET formation, that the priming of neutrophils toward NETosis favors tumor growth. Interestingly, in a tumor model that does not release G-CSF and in which neutrophils are not primed for NETosis, PAD4-deficiency did not reduce tumor growth. However, supplying exogenous G-CSF to the wild-type (WT) host promoted intratumoral NETosis and tumor growth. Taken together, our results suggest that the priming of neutrophils for NETosis by the tumor or its environment leads to the accumulation of intratumoral NETs and a growth advantage to the tumor. Our work unveiled a pro-tumoral role for NETs which strengthens their potential as a new target in the fight against cancer.
authors.affiliation: Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Demers
authors.affiliation: Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
authors.forename: Siu Ling
authors.initials: SL
authors.lastname: Wong
authors.affiliation: Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Martinod
authors.affiliation: Program in Cellular and Molecular Medicine, Boston Children's Hospital , Boston, MA, USA.
authors.forename: Maureen
authors.initials: M
authors.lastname: Gallant
authors.affiliation: Program in Cellular and Molecular Medicine, Boston Children's Hospital , Boston, MA, USA.
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Cabral
authors.affiliation: Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology, Pennsylvania State University , University Park, PA, USA.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Denisa D
authors.initials: DD
authors.lastname: Wagner
keywords: Cancer; G-CSF; NETs; neutrophils; tumor growth