title: B7-H6-mediated downregulation of NKp30 in NK cells contributes to ovarian carcinoma immune escape.
abstract: In this study the phenotype and function of tumor-associated NK cells from peritoneal fluids of a selected cohort of patients with seropapillary ovarian carcinoma were analyzed. In > 50% of these patients, the expression of the activating receptor NKp30 in tumor-associated NK cells was substantially reduced as compared to autologous peripheral blood (PB) NK cells. The impaired expression of this receptor was associated with the presence of one of its cellular ligands (B7-H6), which was detectable as a surface/cytosolic molecule in tumor cells and as a soluble molecule in the peritoneal fluid. NK cells from patients expressing this NKp30low phenotype displayed an impaired interferon-gamma (IFNγ) production and cytolytic function when tested against target cells expressing surface B7-H6. Our data also suggest that in these patients, the defective expression and function of NKp30 may be induced by the chronic engagement of this receptor by soluble B7-H6 or by tumor cells expressing this ligand. The impairment of NK cell functions described herein could represent a novel mechanism by which the tumor microenvironment may contribute to the escape from immune surveillance.
authors.affiliation: Dipartimento di Medicina Sperimentale and Centro di Eccellenza per le Ricerche Biomediche; Università degli Studi di Genova ; Genova, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Pesce
authors.affiliation: Dipartimento di Medicina Molecolare e Traslazionale ; Brescia, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tabellini
authors.affiliation: Istituto Giannina Gaslini ; Genova, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Cantoni
authors.affiliation: Dipartimento di Medicina Molecolare e Traslazionale ; Brescia, Italy.
authors.forename: Ornella
authors.initials: O
authors.lastname: Patrizi
authors.affiliation: Dipartimento di Medicina Molecolare e Traslazionale ; Brescia, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Coltrini
authors.affiliation: Dipartimento di Ostetricia e Ginecologia; Spedali Civili di Brescia ; Brescia, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Rampinelli
authors.affiliation: Centre d'Immunologie de Marseille-Luminy; UM2 Aix-Marseille Université; INSERM, CNRS ; Marseille, France ; Service d'Immunologie; Assistance Publique-Hôpitaux de Marseille; Hôpital de la Conception ; Marseille, France.
authors.forename: Jessica
authors.initials: J
authors.lastname: Matta
authors.affiliation: Centre d'Immunologie de Marseille-Luminy; UM2 Aix-Marseille Université; INSERM, CNRS ; Marseille, France ; Service d'Immunologie; Assistance Publique-Hôpitaux de Marseille; Hôpital de la Conception ; Marseille, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.affiliation: Dipartimento di Medicina Sperimentale and Centro di Eccellenza per le Ricerche Biomediche; Università degli Studi di Genova ; Genova, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.affiliation: Dipartimento di Medicina Molecolare e Traslazionale ; Brescia, Italy ; Service d'Immunologie; Assistance Publique-Hôpitaux de Marseille; Hôpital de la Conception ; Marseille, France.
authors.forename: Silvia
authors.initials: S
authors.lastname: Parolini
authors.affiliation: Dipartimento di Medicina Sperimentale and Centro di Eccellenza per le Ricerche Biomediche; Università degli Studi di Genova ; Genova, Italy ; Service d'Immunologie; Assistance Publique-Hôpitaux de Marseille; Hôpital de la Conception ; Marseille, France.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Marcenaro
keywords: B7-H6; NK cells; NKp30; mechanism of escape; ovarian carcinoma