title: Origin and Role of a Subset of Tumor-Associated Neutrophils with Antigen-Presenting Cell Features in Early-Stage Human Lung Cancer.
abstract: Based on studies in mouse tumor models, granulocytes appear to play a tumor-promoting role. However, there are limited data about the phenotype and function of tumor-associated neutrophils (TANs) in humans. Here, we identify a subset of TANs that exhibited characteristics of both neutrophils and antigen-presenting cells (APCs) in early-stage human lung cancer. These APC-like "hybrid neutrophils," which originate from CD11b(+)CD15(hi)CD10(-)CD16(low) immature progenitors, are able to cross-present antigens, as well as trigger and augment anti-tumor T cell responses. Interferon-γ and granulocyte-macrophage colony-stimulating factor are requisite factors in the tumor that, working through the Ikaros transcription factor, synergistically exert their APC-promoting effects on the progenitors. Overall, these data demonstrate the existence of a specialized TAN subset with anti-tumor capabilities in human cancer.
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Division of Thoracic Surgery, Department of Surgery, Philadelphia VA Medical Center, Philadelphia, PA 19104, USA.
authors.forename: Sunil
authors.initials: S
authors.lastname: Singhal
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Pratik S
authors.initials: PS
authors.lastname: Bhojnagarwala
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Shaun
authors.initials: S
authors.lastname: O'Brien
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Edmund K
authors.initials: EK
authors.lastname: Moon
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Alfred L
authors.initials: AL
authors.lastname: Garfall
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Abhishek S
authors.initials: AS
authors.lastname: Rao
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Jon G
authors.initials: JG
authors.lastname: Quatromoni
authors.affiliation: Tumor Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Tom Li
authors.initials: TL
authors.lastname: Stephen
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Litzky
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Charuhas
authors.initials: C
authors.lastname: Deshpande
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Feldman
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Wayne W
authors.initials: WW
authors.lastname: Hancock
authors.affiliation: Tumor Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Conejo-Garcia
authors.affiliation: Division of Pulmonary, Allergy, and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Albelda
authors.affiliation: Division of Thoracic Surgery, Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: evgeniy.eruslanov@uphs.upenn.edu.
authors.forename: Evgeniy B
authors.initials: EB
authors.lastname: Eruslanov
mesh_terms: D000938:Antigen-Presenting Cells / Q000276:immunology*; D015972:Gene Expression Regulation, Neoplastic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D051740:Ikaros Transcription Factor / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology; D008175:Lung Neoplasms / Q000276:immunology*; D009367:Neoplasm Staging; D009504:Neutrophils / Q000166:cytology / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D051740:Ikaros Transcription Factor; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor