Mañana, JUEVES, 24 DE ABRIL, el sistema se apagará debido a tareas habituales de mantenimiento a partir de las 9 de la mañana. Lamentamos las molestias.
In vitro natural killer cell immunotherapy for medulloblastoma
Entity
UAM. Departamento de Anatomía PatológicaPublisher
FrontiersDate
2013-12-24Citation
10.3389/fonc.2013.00094
Frontiers in Oncology 3 (2013): 94
ISSN
2234-943XDOI
10.3389/fonc.2013.00094Funded by
This work was supported in part by the National Health Serviceof Spain grant FIS PS09/02393 and CRIS Cancer FoundationProject
Gobierno de España. FIS PS09/02393Editor's Version
http://dx.doi.org/10.3389/fonc.2013.00094Subjects
HLA-I; Medulloblastoma; Natural killer cells; NKG2D ligands; NKG2D receptor; MedicinaRights
© 2013 Fernández, Portugal, Valentín, Martín, Maxwell, González- Vicent,Díaz ,de Prada and Pérez- MartínezAbstract
How the immune system attacks medulloblastoma (MB) tumors effectively is unclear,
although natural killer (NK) cells play an important role in immune defense against tumor
cells. Interactions between receptors on NK cells and ligands expressed by tumor cells are
critical for tumor control by immunotherapy. In this study, we analyzed tumor samples from
54 MB patients for expression of major histocompatibility complex class I-related chains
A (MICA) and UL16 binding protein (ULPB-2), which are ligands for the NK group 2 member
D activatory receptor (NKG2D).The percentage of MICA and ULBP-2 positive cells was
higher than 25% in 68% and 6% of MB patients, respectively. A moderate-high intensity of
MICA cytoplasmic staining was observed in 46% MB patients and weak ULBP-2 staining
was observed in 8% MB patients. No correlation between MICA/ULBP-2 expression and
patient outcome was found.We observed that HTB-186, a MB cell line, was moderately
resistant to NK cell cytotoxicity in vitro. Blocking MICA/ULBP-2 on HTB-186, and NKG2D
receptor on NK cells increased resistance to NK cell lysis in vitro. However, HLA class
I blocking on HTB-186 and overnight incubation with IL-15 stimulated NK cells efficiently
killed tumor cells in vitro. We conclude that although NKG2D/MICA-ULBP-2 interactions
have a role in NK cell cytotoxicity against MB, high expression of HLA class I can protect
MB from NK cell cytotoxicity. Even so, our in vitro data indicate that if NK cells are
appropriately stimulated, they may have the potential to target MB in vivo
Files in this item
Google Scholar:Fernández, Lucía G.
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Portugal, Raquel
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Valentín, Jaime
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Martín, Roberto
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Maxwell, Hannah
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González-Vicent, Marta
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Díaz, Miguel Ángel Ruíz
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De Prada, Inmaculada
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Pérez Martínez, Antonio
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