Open AccessProlonged contact with dendritic cells turns lymph node‐resident NK cells into anti‐tumor effectors
Author(s) -
Mingozzi Francesca,
Spreafico Roberto,
Gorletta Tatiana,
Cigni Clara,
Di Gioia Marco,
Caccia Michele,
Sironi Laura,
Collini Maddalena,
Soncini Matias,
Rusconi Michela,
von Andrian Ulrich H,
Chirico Giuseppe,
Zai Ivan,
Granucci Francesca
Publication year - 2016
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201506164
Subject(s) - lymph node , microbiology and biotechnology , lymph , innate lymphoid cell , lymphokine activated killer cell , interleukin 12 , interleukin 21 , immunology , dendritic cell , nk 92 , lymph node stromal cell , antigen presenting cell , biology , janus kinase 3 , cell , innate immune system , cancer research , t cell , immune system , medicine , cytotoxic t cell , pathology , in vitro , biochemistry , genetics
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 ( DC s) 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.