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Status: Bibliographieeintrag

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Verfasst von:Audenaerde, Jonas R. M. van [VerfasserIn]   i
 Jesenofsky, Ralf [VerfasserIn]   i
Titel:Interleukin-15 stimulates natural killer cell-mediated killing of both human pancreatic cancer and stellate cells
Verf.angabe:Jonas R.M. Van Audenaerde, Jorrit De Waele, Elly Marcq, Jinthe Van Loenhout, Eva Lion, Johan M.J. Van den Bergh, Ralf Jesenofsky, Atsushi Masamune, Geert Roeyen, Patrick Pauwels, Filip Lardon, Marc Peeters, Evelien L.J. Smits, Jonas R.M. Van Audenaerde, Jorrit De Waele, Elly Marcq, Jinthe Van Loenhout, Eva Lion, Johan M.J. Van den Bergh, Ralf Jesenofsky, Atsushi Masamune, Geert Roeyen, Patrick Pauwels, Filip Lardon, Marc Peeters and Evelien L.J. Smits
E-Jahr:2017
Jahr:May 25, 2017
Umfang:12 S.
Fussnoten:Gesehen am 16.07.2018
Titel Quelle:Enthalten in: OncoTarget
Ort Quelle:[Erscheinungsort nicht ermittelbar] : Impact Journals LLC, 2010
Jahr Quelle:2017
Band/Heft Quelle:8(2017), 34, Seite 56968-56979
ISSN Quelle:1949-2553
Abstract:Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer-related death in Western countries with a 5-year survival rate below 5%. One of the hallmarks of this cancer is the strong desmoplastic reaction within the tumor microenvironment (TME), orchestrated by activated pancreatic stellate cells (PSC). This results in a functional and mechanical shield which causes resistance to conventional therapies. Aiming to overcome this resistance by tackling the stromal shield, we assessed for the first time the capacity of IL-15 stimulated natural killer (NK) cells to kill PSC and pancreatic cancer cells (PCC). The potency of IL-15 to promote NK cell-mediated killing was evaluated phenotypically and functionally. In addition, NK cell and immune checkpoint ligands on PSC were charted. We demonstrate that IL-15 activated NK cells kill both PCC and PSC lines (range 9-35% and 20-50%, respectively) in a contact-dependent manner and significantly higher as compared to resting NK cells. Improved killing of these pancreatic cell lines is, at least partly, dependent on IL-15 induced upregulation of TIM-3 and NKG2D. Furthermore, we confirm significant killing of primary PSC by IL-15 activated NK cells in an ex vivo autologous system. Screening for potential targets for immunotherapeutic strategies, we demonstrate surface expression of both inhibitory (PD-L1, PD-L2) and activating (MICA/B, ULBPs and Galectin-9) ligands on primary PSC. These data underscore the therapeutic potential of IL-15 to promote NK cell-mediated cytotoxicity as a treatment of pancreatic cancer and provide promising future targets to tackle remaining PSC.
DOI:doi:10.18632/oncotarget.18185
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

kostenfrei: Volltext: http://dx.doi.org/10.18632/oncotarget.18185
 kostenfrei: Volltext: http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=18185&path[]=59002
 DOI: https://doi.org/10.18632/oncotarget.18185
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:1577645324
Verknüpfungen:→ Zeitschrift

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