NK cells from malignant pleural effusions are not anergic but produce cytokines and display strong anti-tumor activity on short-term IL-2 activation.
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1
University of Genoa, Genoa, Italy, DIMES, Italy
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2
IRCCS AOU San Martino-IST (National Institute for Cancer Research), Genova, Italy, Italy
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3
Giannina Gaslini Institute, Genova, Italy.University of Genoa, Genoa, Italy, Italy
NK cells are a major component of the innate immunity and exert a potent anti-tumor effect both in vitro and in vivo. However, tumor infiltrating natural killer (NK) cells have been shown to display severely impaired functional properties. In this study, we analyzed NK cells isolated from pleural effusions (PE) in patients with primary or metastatic tumors of different origin (including mesotheliomas, lung carcinomas, breast, colon gastric and liver carcinomas). Freshly isolated PE-NK cells displayed a CD56bright phenotype and expressed normal levels of both activating receptors and HLA-Class I-specific inhibitory receptors. In addition, they rapidly released large amounts of IFN-γ and TNF-α upon stimulation. After short- or long-term culture in IL-2, they acquired a potent cytolytic activity against both allogenic and autologous tumor cells. Tumor cell lysis was primarily mediated by NKG2D and by NKp30 and, in part, by NKp46 and DNAM-1, in agreement with the expression of the corresponding ligands on tumor cells. The finding that PE-NK cells are not functionally impaired and can efficiently kill tumor cells upon IL-2 activation may offer an important clue for novel approaches in tumor immunotherapy.
References
NK cells from malignant pleural effusions are not anergic but produce cytokines and display strong antitumor activity on short-term IL-2 activation.
Vacca P, Martini S, Garelli V, Passalacqua G, Moretta L, Mingari MC.
Eur J Immunol. 2013 Feb;43(2):550-61. doi: 10.1002/eji.201242783. Epub 2013 Jan 15.
NK cells from malignant pleural effusions are potent antitumor effectors: A clue for adoptive immunotherapy?
Vacca P, Martini S, Mingari MC, Moretta L.
Oncoimmunology. 2013 Apr 1;2(4):e23638.
Keywords:
NK,
Immunotherapy,
IL2,
Mesothelioma,
Pleural Effusion
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Innate immunity
Citation:
Vacca
P,
Martini
S,
Moretta
L and
Mingari
M
(2013). NK cells from malignant pleural effusions are not anergic but produce cytokines and display strong anti-tumor activity on short-term IL-2 activation..
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00995
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Received:
26 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Paola Vacca, University of Genoa, Genoa, Italy, DIMES, Genoa, Italy, paola.vacca@opbg.net
Prof. Lorenzo Moretta, Giannina Gaslini Institute, Genova, Italy.University of Genoa, Genoa, Italy, Genoa, Italy, lorenzo.moretta@opbg.net