1. Prolonged contact with dendritic cells turns lymph node‐resident <scp>NK</scp> cells into anti‐tumor effectors
- Author
-
Francesca Mingozzi, Tatiana Gorletta, Francesca Granucci, Clara Cigni, Michela Rusconi, Giuseppe Chirico, Marco Di Gioia, Ivan Zanoni, Michele Caccia, Laura Sironi, Roberto Spreafico, Matias Cristobal Soncini, Ulrich H. von Andrian, Maddalena Collini, Mingozzi, F, Spreafico, R, Gorletta, T, Cigni, C, DI GIOIA, M, Caccia, M, Sironi, L, Collini, M, Soncini, M, Rusconi, M, von Andrian, U, Chirico, G, Zanoni, I, and Granucci, F
- Subjects
Lipopolysaccharides ,0301 basic medicine ,Lipopolysaccharide ,Immunology ,Natural killer cell ,immunosurveillance ,Biology ,Lymphocyte Activation ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,Interleukin 21 ,0302 clinical medicine ,NK-92 ,Neoplasms ,medicine ,Animals ,two‐photon microscopy ,Two-photon microscopy ,innate immunity ,Lymph node ,Research Articles ,Cancer ,natural killer cells ,Innate immune system ,Dendritic Cells ,3. Good health ,Killer Cells, Natural ,Immunosurveillance ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,MED/06 - ONCOLOGIA MEDICA ,Interleukin 12 ,Molecular Medicine ,Lymph Nodes ,Lymph ,Dendritic cell ,Research Article ,030215 immunology - 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.
- Published
- 2016
- Full Text
- View/download PDF