title: CD11b+Ly6G+ cells inhibit tumor growth by suppressing IL-17 production at early stages of tumorigenesis.
abstract: Neutrophils are important innate immune cells involved in microbial clearance at the sites of infection. However, their role in cancer development is unclear. We hypothesized that neutrophils mediate antitumor effects in early tumorigenesis. To test this, we first studied the cytotoxic effects of neutrophilsin vitro. Neutrophils were cytotoxic against tumor cells, with neutrophils isolated from tumor-bearing mice trending to have increased cytotoxic activities. We then injected an ELR+ CXC chemokine-producing tumor cell line into C57BL/6 andCxcr2-/-mice, the latter lacking the receptors for neutrophil chemokines. We observed increased tumor growth inCxcr2-/-mice. As expected, tumors fromCxcr2-/-mice contained fewer neutrophils. Surprisingly, these tumors also contained fewer CD8+T cells, but more IL-17-producing cells. Replenishment of functional neutrophils was correlated with decreased IL-17-producing cells, increased CD8+T cells, and decreased tumor size inCxcr2-/-mice, while depletion of neutrophils in C57BL/6 mice showed the opposite effects. Results from a non-ELR+ CXC chemokine producing tumor further supported that functional neutrophils indirectly mediate tumor control by suppressing IL-17A production. We further studied the correlation of IL-17A and CD8+T cellsin vitro. IL-17A suppressed proliferation and IFNγ production of CD8+T cells, while CD11b+Ly6G+ neutrophils did not suppress CD8+T cell function. Taken together, these data demonstrate that, while neutrophils could control tumor growth by direct cytotoxic effects, the primary mechanism by which neutrophils exert antitumor effects is to regulate IL-17 production, through which they indirectly promote CD8+T cell responses.
authors.affiliation: Division of Neonatology; Children's Hospital of Philadelphia ; Philadelphia, PA USA.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Perelman School of Medicine; University of Pennsylvania ; Philadelphia, PA USA.
authors.forename: Claire E
authors.initials: CE
authors.lastname: O'Leary
authors.affiliation: Division of Pulmonary; Allergy and Critical Care Medicine; Department of Medicine; Perelman School of Medicine at the University of Pennsylvania ; Philadelphia, PA USA.
authors.forename: Liang-Chuan S
authors.initials: LS
authors.lastname: Wang
authors.affiliation: Department of Pathology and Laboratory Medicine; Children's Hospital of Philadelphia ; Philadelphia, PA USA.
authors.forename: Tricia R
authors.initials: TR
authors.lastname: Bhatti
authors.affiliation: Division of Neonatology; Children's Hospital of Philadelphia ; Philadelphia, PA USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Dai
authors.affiliation: Division of Pulmonary; Allergy and Critical Care Medicine; Department of Medicine; Perelman School of Medicine at the University of Pennsylvania ; Philadelphia, PA USA.
authors.forename: Veena
authors.initials: V
authors.lastname: Kapoor
authors.affiliation: Department of Pediatrics; Affiliated Shenzhen Maternity & Healthcare Hospital of Southern Medical University ; Shenzhen, China.
authors.forename: Peihui
authors.initials: P
authors.lastname: Liu
authors.affiliation: Division of Neonatology; Children's Hospital of Philadelphia; Philadelphia, PA USA; Institute of Medical Biology; Chinese Academy of Medical Sciences; Peking Union Medical College; Kunming, Yunnan Province, P. R. China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Mei
authors.affiliation: Institute of Medical Biology; Chinese Academy of Medical Sciences; Peking Union Medical College ; Kunming, Yunnan Province, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
authors.affiliation: Perelman School of Medicine; University of Pennsylvania; Philadelphia, PA USA; Cell Pathology Division; Department of Pathology and Laboratory Medicine; Children's Hospital of Philadelphia; Philadelphia, PA USA.
authors.forename: Paula M
authors.initials: PM
authors.lastname: Oliver
authors.affiliation: Division of Pulmonary; Allergy and Critical Care Medicine; Department of Medicine; Perelman School of Medicine at the University of Pennsylvania ; Philadelphia, PA USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Albelda
authors.affiliation: Division of Neonatology; Children's Hospital of Philadelphia; Philadelphia, PA USA; Department of Pediatrics; Perelman School of Medicine; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: G Scott
authors.initials: GS
authors.lastname: Worthen
keywords: CD11b+Ly6G+Cells, Neutrophils, Tumor, IL-17 and CD8+T cells