期刊
EMBO MOLECULAR MEDICINE
卷 8, 期 9, 页码 1039-1051出版社
WILEY
DOI: 10.15252/emmm.201506164
关键词
dendritic cells; immunosurveillance; innate immunity; natural killer cells; two-photon microscopy
资金
- Associazione Italiana per la Ricerca sul Cancro (AIRC) [IG14593]
- Fondazione Cariplo [2014-0655, 2014-0859, 2013-0624]
- ARISLA (grant DC-ALS)
- Fondazione Regionale per la Ricerca Biomedica (FRRB)
- NIH [1R01AI121066-01A1]
- CCFA [412708]
- Harvard University Milton Fund
- HDDC [P30 DK034854]
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.
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