PT  - JOURNAL ARTICLE
AU  - Semeraro, Michaela
AU  - Rusakiewicz, Sylvie
AU  - Minard-Colin, Véronique
AU  - Delahaye, Nicolas F.
AU  - Enot, David
AU  - Vély, Frédéric
AU  - Marabelle, Aurélien
AU  - Papoular, Benjamin
AU  - Piperoglou, Christelle
AU  - Ponzoni, Mirco
AU  - Perri, Patrizia
AU  - Tchirkov, Andrei
AU  - Matta, Jessica
AU  - Lapierre, Valérie
AU  - Shekarian, Tala
AU  - Valsesia-Wittmann, Sandrine
AU  - Commo, Frédéric
AU  - Prada, Nicole
AU  - Poirier-Colame, Vichnou
AU  - Bressac, Brigitte
AU  - Cotteret, Sophie
AU  - Brugieres, Laurence
AU  - Farace, Françoise
AU  - Chaput, Nathalie
AU  - Kroemer, Guido
AU  - Valteau-Couanet, Dominique
AU  - Zitvogel, Laurence
TI  - Clinical impact of the NKp30/B7-H6 axis in high-risk neuroblastoma patients
AID  - 10.1126/scitranslmed.aaa2327
DP  - 2015 Apr 15
TA  - Science Translational Medicine
PG  - 283ra55--283ra55
VI  - 7
IP  - 283
4099  - http://stm.sciencemag.org/content/7/283/283ra55.short
4100  - http://stm.sciencemag.org/content/7/283/283ra55.full
AB  - Natural killer cells, a part of the innate immune system, can kill cancer cells. Neuroblastoma is a common pediatric cancer that is difficult to treat, especially in older children with metastatic disease. The immune system helps to control the spread of neuroblastoma, and immune-based treatments for this cancer are under active investigation. Now, Semeraro et al. analyzed the role of natural killer cells in neuroblastoma and sought to understand why they are not always equally effective against the tumor. The authors found that the key lies in the predominant isoform of a receptor that natural killer cells use to interact with neuroblastoma cells and that the balance between isoforms of this receptor on a patient’s cells can help predict survival.The immunosurveillance mechanisms governing high-risk neuroblastoma (HR-NB), a major pediatric malignancy, have been elusive. We identify a potential role for natural killer (NK) cells, in particular the interaction between the NK receptor NKp30 and its ligand, B7-H6, in the metastatic progression and survival of HR-NB after myeloablative multimodal chemotherapy and stem cell transplantation. NB cells expressing the NKp30 ligand B7-H6 stimulated NK cells in an NKp30-dependent manner. Serum concentration of soluble B7-H6 correlated with the down-regulation of NKp30, bone marrow metastases, and chemoresistance, and soluble B7-H6 contained in the serum of HR-NB patients inhibited NK cell functions in vitro. The expression of distinct NKp30 isoforms affecting the polarization of NK cell functions correlated with 10-year event-free survival in three independent cohorts of HR-NB in remission from metastases after induction chemotherapy (n = 196, P < 0.001), adding prognostic value to known risk factors such as N-Myc amplification and age >18 months. We conclude that the interaction between NKp30 and B7-H6 may contribute to the fate of NB patients and that both the expression of NKp30 isoforms on circulating NK cells and the concentration of soluble B7-H6 in the serum may be clinically useful as biomarkers for risk stratification.