title: Natural killer cell mediated immunosurveillance of pediatric neuroblastoma.
abstract: Until recently, the pathophysiological impact of natural killer (NK) lymphocytes has been largely elusive. Capitalizing on our previous discovery that NK cells mediate immunosurveillance against gastrointestinal stromal tumors (GISTs), we have now investigated the potential influence of immunostimulatory and immunosuppressive isoforms of the NK receptor NKp30 on the fate of infants with neuroblastoma. In three independent cohorts of high-risk neuroblastoma, we observed a similar prognostic impact of the ratio of immunostimulatory vs. immunosuppressive NKp30 isoforms. Patients with high-risk neuroblastoma that are in remission after induction chemotherapy have a higher risk of relapse if their circulating and bone marrow NK cells express the preponderantly immunosuppressive NKp30 C isoform, as determined by a robust RT-PCR-based assay. We also found that neuroblastoma cells express the NKp30 ligand B7-H6, which can be shed from the tumor cells. Elevated soluble B7-H6 levels contained in patient sera inhibited NK functionsin vitroand correlated with downregulation of NK-p30 on NK cells, as well as with bone marrow metastasis and chemoresistance. Altogether, these results support the contention that NK cells play a decisive role in the immunosurveillance of neuroblastoma. In light of these results, efforts should be undertaken to investigate NK cell functions in all major cancer types, with the obvious expectation of identifying additional NK cell-related prognostic or predictive biomarkers and improving NK cell based immunotherapeutic strategies against cancer.
authors.affiliation: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC) ; Villejuif, France ; INSERM U1015; GRCC ; Villejuif, France ; Department of Pediatric Oncology; GRCC ; Villejuif, France ; University of Paris Sud XI ; Villejuif, France ; Equipe 11 labelisée par la Ligue Nationale contre le Cancer; Centre de Recherche des Cordeliers ; Paris, France ; INSERM U1138; 94805 Centre de Recherche des Cordeliers ; Paris, France ; Center of Clinical Investigations in Biotherapies of Cancer; CICBT507; GRCC , Villejuif, France.
authors.forename: Michaela
authors.initials: M
authors.lastname: Semeraro
authors.affiliation: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC) ; Villejuif, France ; INSERM U1015; GRCC ; Villejuif, France ; Department of Pediatric Oncology; GRCC ; Villejuif, France ; University of Paris Sud XI ; Villejuif, France ; Equipe 11 labelisée par la Ligue Nationale contre le Cancer; Centre de Recherche des Cordeliers ; Paris, France ; INSERM U1138; 94805 Centre de Recherche des Cordeliers ; Paris, France ; Center of Clinical Investigations in Biotherapies of Cancer; CICBT507; GRCC , Villejuif, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rusakiewicz
authors.affiliation: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC) ; Villejuif, France ; INSERM U1015; GRCC ; Villejuif, France ; Department of Pediatric Oncology; GRCC ; Villejuif, France ; University of Paris Sud XI ; Villejuif, France ; Equipe 11 labelisée par la Ligue Nationale contre le Cancer; Centre de Recherche des Cordeliers ; Paris, France ; INSERM U1138; 94805 Centre de Recherche des Cordeliers ; Paris, France ; Center of Clinical Investigations in Biotherapies of Cancer; CICBT507; GRCC , Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.affiliation: Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC) ; Villejuif, France ; INSERM U1015; GRCC ; Villejuif, France ; Department of Pediatric Oncology; GRCC ; Villejuif, France ; University of Paris Sud XI ; Villejuif, France ; Equipe 11 labelisée par la Ligue Nationale contre le Cancer; Centre de Recherche des Cordeliers ; Paris, France ; INSERM U1138; 94805 Centre de Recherche des Cordeliers ; Paris, France ; Center of Clinical Investigations in Biotherapies of Cancer; CICBT507; GRCC , Villejuif, France ; Sorbonne Paris Cité; University of Paris Descartes ; Paris, France ; University of Paris Pierre & Marie Curie ; Paris, France ; ; Pôle de Biologie; Hôpital Européen Georges Pompidou ; Paris, France ; Metabolomics and Cell Biology Platforms; GRCC ; Villejuif, France.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
keywords: NK cells; NKp30; immunosurveillance; neuroblastoma; pediatric cancer