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EMBO Mol Med. 2016 Sep 1;8(9):1039-51. doi: 10.15252/emmm.201506164. Print 2016 Sep.

Prolonged contact with dendritic cells turns lymph node-resident NK cells into anti-tumor effectors.

Author information

1
Department of Biotechnology and Biosciences, University of Milano-Bicocca, Milan, Italy.
2
Harvard Medical School and Division of Gastroenterology, Boston Children's Hospital, Boston, MA, USA.
3
Department of Physics, University of Milano-Bicocca, Milan, Italy.
4
Humanitas Clinical and Research Center, Rozzano (MI), Italy.
5
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA The Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
6
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.
7
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.

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.

KEYWORDS:

dendritic cells; immunosurveillance; innate immunity; natural killer cells; two‐photon microscopy

PMID:
27406819
PMCID:
PMC5009809
DOI:
10.15252/emmm.201506164
[Indexed for MEDLINE]
Free PMC Article

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