RESUMEN
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.
Asunto(s)
Antígenos B7/metabolismo , Neoplasias Encefálicas/metabolismo , Regulación Neoplásica de la Expresión Génica , Receptor 3 Gatillante de la Citotoxidad Natural/metabolismo , Neuroblastoma/metabolismo , Adolescente , Adulto , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor , Neoplasias Encefálicas/mortalidad , Línea Celular Tumoral , Niño , Preescolar , Supervivencia sin Enfermedad , Humanos , Lactante , Células Jurkat , Ligandos , Metástasis de la Neoplasia , Neuroblastoma/mortalidad , Fenotipo , Pronóstico , Estudios Prospectivos , Unión Proteica , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: Since the last recommendations, up to 2,500 new references had been published on that topic. METHODOLOGY: On the behalf of the health Minister, the Ad Hoc Committee consisted of 13 experts carried out a first version revisited by five additional experts who critically analyzed the first version of the report. MAIN UPDATING: Breast and ovarian cancer seem to be associated with fewer deleterious mutation of BRCA12 and BRCA2 than previously thought. The screening of ovarian cancer is still not an attractive option while in contrast MRI may be soon for these young women with dense breast, the recommended option for breast cancer screening. The effectiveness of prophylactic surgeries is now well established. French position is to favor such surgeries with regard to a quality of life in line with the expected benefit, and providing precise and standardized process described in the recommendation. CONCLUSIONS: Due to methodological flaws, the low power and a short follow-up of the surveys, this statement cannot however aspire to a high stability.