TY - JOUR
T1 - Clinical impact of the NKp30/B7-H6 axis in high-risk neuroblastoma patients
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
PY - 2015/4/15
Y1 - 2015/4/15
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84928253171&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.aaa2327
DO - 10.1126/scitranslmed.aaa2327
M3 - Article
C2 - 25877893
AN - SCOPUS:84928253171
SN - 1946-6234
VL - 7
JO - Science Translational Medicine
JF - Science Translational Medicine
IS - 283
M1 - 283ra55
ER -