title: Prolonged contact with dendritic cells turns lymph node-resident NK cells into anti-tumor effectors.
abstract: Natural killer (NK) cells are critical players against tumors. The outcome of anti-tumor vaccination protocols depends on the efficiency of NK-cell activation, and efforts are constantly made to manipulate them for immunotherapeutic approaches. Thus, a better understanding of NK-cell activation dynamics is needed. NK-cell interactions with accessory cells and trafficking between secondary lymphoid organs and tumoral tissues remain poorly characterized. Here, we show that upon triggering innate immunity with lipopolysaccharide (LPS), NK cells are transiently activated, leave the lymph node, and infiltrate the tumor, delaying its growth. Interestingly, NK cells are not actively recruited at the draining lymph node early after LPS administration, but continue their regular homeostatic turnover. Therefore, NK cells resident in the lymph node at the time of LPS administration become activated and exert anti-tumor functions. NK-cell activation correlates with the establishment of prolonged interactions with dendritic cells (DCs) in lymph nodes, as observed by two-photon microscopy. Close DC and NK-cell contacts are essential for the localized delivery of DC-derived IL-18 to NK cells, a strict requirement in NK-cell activation.
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mingozzi
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Spreafico
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Gorletta
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Cigni
authors.affiliation: Harvard Medical School and Division of Gastroenterology, Boston Children's Hospital, Boston, MA, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Di Gioia
authors.affiliation: Department of Physics, University of Milano-Bicocca, Milan, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Caccia
authors.affiliation: Department of Physics, University of Milano-Bicocca, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Sironi
authors.affiliation: Department of Physics, University of Milano-Bicocca, Milan, Italy.
authors.forename: Maddalena
authors.initials: M
authors.lastname: Collini
authors.affiliation: Humanitas Clinical and Research Center, Rozzano (MI), Italy.
authors.forename: Matias
authors.initials: M
authors.lastname: Soncini
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Rusconi
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA The Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: von Andrian
authors.affiliation: Department of Physics, University of Milano-Bicocca, Milan, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Chirico
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy Harvard Medical School and Division of Gastroenterology, Boston Children's Hospital, Boston, MA, USA Humanitas Clinical and Research Center, Rozzano (MI), Italy ivan.zanoni@childrens.harvard.edu francesca.granucci@unimib.it.
authors.forename: Ivan
authors.initials: I
authors.lastname: Zanoni
authors.affiliation: Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy Humanitas Clinical and Research Center, Rozzano (MI), Italy ivan.zanoni@childrens.harvard.edu francesca.granucci@unimib.it.
authors.forename: Francesca
authors.identifier: 0000-0002-7046-4914
authors.initials: F
authors.lastname: Granucci
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D007694:Killer Cells, Natural / Q000276:immunology*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D009369:Neoplasms / Q000276:immunology / Q000473:pathology*
chemical_list: D008070:Lipopolysaccharides
keywords: dendritic cells; immunosurveillance; innate immunity; natural killer cells; two‐photon microscopy