TY - JOUR
T1 - Prolonged contact with dendritic cells turns lymph node-resident NK cells into anti-tumor effectors
AU - Mingozzi, Francesca
AU - Spreafico, Roberto
AU - Gorletta, Tatiana
AU - Cigni, Clara
AU - Di Gioia, Marco
AU - Caccia, Michele
AU - Sironi, Laura
AU - Collini, Maddalena
AU - Soncini, Matias Cristobal
AU - Rusconi, Michela
AU - von Andrian, Ulrich H.
AU - Chirico, Giuseppe
AU - Zanoni, Ivan
AU - Granucci, Francesca
PY - 2016/9/1
Y1 - 2016/9/1
N2 - 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.
AB - 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.
KW - dendritic cells
KW - immunosurveillance
KW - innate immunity
KW - natural killer cells
KW - two-photon microscopy
UR - http://www.scopus.com/inward/record.url?scp=84984850960&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84984850960&partnerID=8YFLogxK
U2 - 10.15252/emmm.201506164
DO - 10.15252/emmm.201506164
M3 - Article
VL - 8
SP - 1039
EP - 1051
JO - EMBO Molecular Medicine
JF - EMBO Molecular Medicine
SN - 1757-4676
IS - 9
ER -