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Clinical impact of the NKp30/B7-H6 axis in high-risk neuroblastoma patients.
- Source :
-
Science translational medicine [Sci Transl Med] 2015 Apr 15; Vol. 7 (283), pp. 283ra55. - Publication Year :
- 2015
-
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.<br /> (Copyright © 2015, American Association for the Advancement of Science.)
- Subjects :
- Adolescent
Adult
Antineoplastic Agents therapeutic use
Antineoplastic Combined Chemotherapy Protocols therapeutic use
Biomarkers, Tumor
Brain Neoplasms mortality
Cell Line, Tumor
Child
Child, Preschool
Disease-Free Survival
Humans
Infant
Jurkat Cells
Ligands
Neoplasm Metastasis
Neuroblastoma mortality
Phenotype
Prognosis
Prospective Studies
Protein Binding
Risk Factors
Young Adult
B7 Antigens metabolism
Brain Neoplasms metabolism
Gene Expression Regulation, Neoplastic
Natural Cytotoxicity Triggering Receptor 3 metabolism
Neuroblastoma metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1946-6242
- Volume :
- 7
- Issue :
- 283
- Database :
- MEDLINE
- Journal :
- Science translational medicine
- Publication Type :
- Academic Journal
- Accession number :
- 25877893
- Full Text :
- https://doi.org/10.1126/scitranslmed.aaa2327