Clinical impact of the NKp30/B7-H6 axis in high-risk neuroblastoma patients

Michaela Semeraro, Sylvie Rusakiewicz, Véronique Minard-Colin, Nicolas F. Delahaye, David Enot, Frédéric Vély, Aurélien Marabelle, Benjamin Papoular, Christelle Piperoglou, Mirco Ponzoni, Patrizia Perri, Andrei Tchirkov, Jessica Matta, Valérie Lapierre, Tala Shekarian, Sandrine Valsesia-Wittmann, Frédéric Commo, Nicole Prada, Vichnou Poirier-Colame, Brigitte BressacSophie Cotteret, Laurence Brugieres, Françoise Farace, Nathalie Chaput, Guido Kroemer, Dominique Valteau-Couanet, Laurence Zitvogel

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number283ra55
JournalScience Translational Medicine
Volume7
Issue number283
DOIs
Publication statusPublished - Apr 15 2015

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ASJC Scopus subject areas

  • Medicine(all)

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Semeraro, M., Rusakiewicz, S., Minard-Colin, V., Delahaye, N. F., Enot, D., Vély, F., Marabelle, A., Papoular, B., Piperoglou, C., Ponzoni, M., Perri, P., Tchirkov, A., Matta, J., Lapierre, V., Shekarian, T., Valsesia-Wittmann, S., Commo, F., Prada, N., Poirier-Colame, V., ... Zitvogel, L. (2015). Clinical impact of the NKp30/B7-H6 axis in high-risk neuroblastoma patients. Science Translational Medicine, 7(283), [283ra55]. https://doi.org/10.1126/scitranslmed.aaa2327