title: Clinical impact of the NKp30/B7-H6 axis in high-risk neuroblastoma patients.
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.
authors: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, 94805 Villejuif, France. Department of Pediatric Oncology, GRCC, 94805 Villejuif, France. University of Paris Sud XI, 94805 Villejuif, France. Equipe 11 labelisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France. INSERM U1138, 94805 Villejuif, France.
authors: Michaela
authors: M
authors: Semeraro
authors: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, 94805 Villejuif, France. Center of Clinical Investigations in Biotherapies of Cancer, CICBT507, GRCC, 94805 Villejuif, France.
authors: Sylvie
authors: S
authors: Rusakiewicz
authors: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, 94805 Villejuif, France. Department of Pediatric Oncology, GRCC, 94805 Villejuif, France.
authors: Véronique
authors: V
authors: Minard-Colin
authors: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, 94805 Villejuif, France.
authors: Nicolas F
authors: NF
authors: Delahaye
authors: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. Equipe 11 labelisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France. INSERM U1138, 94805 Villejuif, France.
authors: David
authors: D
authors: Enot
authors: Centre d'Immunologie de Marseille-Luminy, INSERM, U1104, F-13009 Marseille, France. CNRS, UMR7280, F-13009 Marseille, France. Aix Marseille Université, UM2, F-13009 Marseille, France. Service d'Immunologie, Assistance Publique-Hôpitaux de Marseille, Hôpital de la Conception, F-13009 Marseille, France.
authors: Frédéric
authors: F
authors: Vély
authors: Centre de Recherche en Cancérologie de Lyon, UMR INSERM U1052 CNRS 5286, Centre Léon Bérard, Université de Lyon, 69000 Lyon, France.
authors: Aurélien
authors: A
authors: Marabelle
authors: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, 94805 Villejuif, France.
authors: Benjamin
authors: B
authors: Papoular
authors: Service d'Immunologie, Assistance Publique-Hôpitaux de Marseille, Hôpital de la Conception, F-13009 Marseille, France.
authors: Christelle
authors: C
authors: Piperoglou
authors: Giannina Gaslini Hospital, Experimental Therapy Unit Laboratory of Oncology, 16147 Genoa, Italy.
authors: Mirco
authors: M
authors: Ponzoni
authors: Giannina Gaslini Hospital, Experimental Therapy Unit Laboratory of Oncology, 16147 Genoa, Italy.
authors: Patrizia
authors: P
authors: Perri
authors: EA 4677 ERTICa, CHU et Centre Jean Perrin, 63011 Clermont-Ferrand, France. CHU de Clermont-Ferrand, Service de Cytogénétique Médicale, Hôpital Estaing, 63001 Clermont-Ferrand, France.
authors: Andrei
authors: A
authors: Tchirkov
authors: Centre d'Immunologie de Marseille-Luminy, INSERM, U1104, F-13009 Marseille, France. CNRS, UMR7280, F-13009 Marseille, France. Aix Marseille Université, UM2, F-13009 Marseille, France.
authors: Jessica
authors: J
authors: Matta
authors: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. Cell Therapy Unit, GRCC, 94805 Villejuif, France.
authors: Valérie
authors: V
authors: Lapierre
authors: Centre de Recherche en Cancérologie de Lyon, UMR INSERM U1052 CNRS 5286, Centre Léon Bérard, Université de Lyon, 69000 Lyon, France.
authors: Tala
authors: T
authors: Shekarian
authors: Centre de Recherche en Cancérologie de Lyon, UMR INSERM U1052 CNRS 5286, Centre Léon Bérard, Université de Lyon, 69000 Lyon, France.
authors: Sandrine
authors: S
authors: Valsesia-Wittmann
authors: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, 94805 Villejuif, France.
authors: Frédéric
authors: F
authors: Commo
authors: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, 94805 Villejuif, France.
authors: Nicole
authors: N
authors: Prada
authors: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, 94805 Villejuif, France.
authors: Vichnou
authors: V
authors: Poirier-Colame
authors: Service de Génétique, Molecular Genetic Department, GRCC, 94805 Villejuif, France.
authors: Brigitte
authors: B
authors: Bressac
authors: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, 94805 Villejuif, France.
authors: Sophie
authors: S
authors: Cotteret
authors: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. Department of Pediatric Oncology, GRCC, 94805 Villejuif, France.
authors: Laurence
authors: L
authors: Brugieres
authors: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U981, 94805 Villejuif, France.
authors: Françoise
authors: F
authors: Farace
authors: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, 94805 Villejuif, France. Center of Clinical Investigations in Biotherapies of Cancer, CICBT507, GRCC, 94805 Villejuif, France.
authors: Nathalie
authors: N
authors: Chaput
authors: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. Equipe 11 labelisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, 75006 Paris, France. INSERM U1138, 94805 Villejuif, France. University of Paris Descartes/ParisV, Sorbonne Paris Cité, 75005 Paris, France. Pôle de Biologie, Hôpital Européen Georges Pompidou, 75015 Paris, France. laurence.zitvogel@gustaveroussy.fr kroemer@orange.fr.
authors: Guido
authors: G
authors: Kroemer
authors: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, 94805 Villejuif, France. Department of Pediatric Oncology, GRCC, 94805 Villejuif, France.
authors: Dominique
authors: D
authors: Valteau-Couanet
authors: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, 94805 Villejuif, France. INSERM U1015, GRCC, 94805 Villejuif, France. University of Paris Sud XI, 94805 Villejuif, France. Center of Clinical Investigations in Biotherapies of Cancer, CICBT507, GRCC, 94805 Villejuif, France. laurence.zitvogel@gustaveroussy.fr kroemer@orange.fr.
authors: Laurence
authors: L
authors: Zitvogel
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D060887:B7 Antigens / Q000378:metabolism*; D014408:Biomarkers, Tumor; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality; D045744:Cell Line, Tumor; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007223:Infant; D019169:Jurkat Cells; D008024:Ligands; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009447:Neuroblastoma / Q000378:metabolism* / Q000401:mortality; D010641:Phenotype; D011379:Prognosis; D011446:Prospective Studies; D011485:Protein Binding; D012307:Risk Factors; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D060887:B7 Antigens; D014408:Biomarkers, Tumor; D008024:Ligands; C431710:NCR3 protein, human; C542363:NCR3LG1 protein, human; D055628:Natural Cytotoxicity Triggering Receptor 3