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

Francesca Mingozzi, Roberto Spreafico, Tatiana Gorletta, Clara Cigni, Marco Di Gioia, Michele Caccia, Laura Sironi, Maddalena Collini, Matias Soncini, Michela Rusconi, Ulrich H. von Andrian, Giuseppe Chirico, Ivan Zanoni, Francesca Granucci

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1039-1051
Number of pages13
JournalEMBO Molecular Medicine
Volume8
Issue number9
DOIs
Publication statusPublished - Sep 1 2016

Keywords

  • dendritic cells
  • immunosurveillance
  • innate immunity
  • natural killer cells
  • two-photon microscopy

ASJC Scopus subject areas

  • Molecular Medicine

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