RT Journal Article
SR Electronic
T1 Clinical impact of the NKp30/B7-H6 axis in high-risk neuroblastoma patients
JF Science Translational Medicine
FD American Association for the Advancement of Science
SP 283ra55
OP 283ra55
DO 10.1126/scitranslmed.aaa2327
VO 7
IS 283
A1 Semeraro, Michaela
A1 Rusakiewicz, Sylvie
A1 Minard-Colin, Véronique
A1 Delahaye, Nicolas F.
A1 Enot, David
A1 Vély, Frédéric
A1 Marabelle, Aurélien
A1 Papoular, Benjamin
A1 Piperoglou, Christelle
A1 Ponzoni, Mirco
A1 Perri, Patrizia
A1 Tchirkov, Andrei
A1 Matta, Jessica
A1 Lapierre, Valérie
A1 Shekarian, Tala
A1 Valsesia-Wittmann, Sandrine
A1 Commo, Frédéric
A1 Prada, Nicole
A1 Poirier-Colame, Vichnou
A1 Bressac, Brigitte
A1 Cotteret, Sophie
A1 Brugieres, Laurence
A1 Farace, Françoise
A1 Chaput, Nathalie
A1 Kroemer, Guido
A1 Valteau-Couanet, Dominique
A1 Zitvogel, Laurence
YR 2015
UL http://stm.sciencemag.org/content/7/283/283ra55.abstract
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.