title: NKp30 isoforms and NKp46 transcripts in metastatic melanoma patients: Unique NKp30 pattern in rare melanoma patients with favorable evolution.
abstract: Given the NK cell-based immunosurveillance of melanoma, we investigated the prognostic value of NKp46 transcript and NKp30 isoform (NKp30A, NKp30B and NKp30C) profiling in blood of 187 melanoma patients including 13 long survivors (LS), metastatic patients that have controlled the disease. Compared to healthy volunteers (HV), patients had reduced amounts of transcripts of the three NKp30 isoforms (NKp30 A, B and C) but similar ratios between NKp30 isoforms (ΔAB, ΔAC, ΔBC). Stratification of patients according to disease stage showed higher NKp30C and lower NKp46 transcripts in stage IV patients. Furthermore, patients with previous history of conventional chemotherapy displayed reduced NKp30A transcripts. The expression levels of NKp30 isoforms failed to predict survival from sampling of patients, while NKp46 expression predicted melanoma outcome. LS patients displayed elevated NKp30A levels, accordingly high ΔAB and ΔBC ratios, and a unique pattern of rare allelic variants of NKp30 SNPs. Moreover, NK cells from LS displayed correlated NKp30/NKp46 membrane expression, high spontaneous and NKp30- or NKp46-triggered degranulation. These data outline the impact of NKp30 and NKp46 transcripts on melanoma evolution and identify unique genetic features of NKp30 associated with higher NK activation in rare LS melanoma patients that control a metastatic disease.
authors.affiliation: INSERMU1160, Institut Universitaire d'Hématologie, Hôpital Saint Louis , Paris, France.
authors.forename: Meriem
authors.initials: M
authors.lastname: Messaoudene
authors.affiliation: Centre Hospitalier Universitaire Vaudois, Faculty of Biology and Medicine, University of Lausanne , Lausanne, Switzerland.
authors.forename: Giulia
authors.initials: G
authors.lastname: Fregni
authors.affiliation: U1015 INSERM-CIC, Institut Gustave Roussy , Villejuif, France.
authors.forename: David
authors.initials: D
authors.lastname: Enot
authors.affiliation: U1015 INSERM-CIC, Institut Gustave Roussy, Villejuif, France; University of Paris Sud XI, Kremlin Bicêtre, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Jacquelot
authors.affiliation: INSERMU1160, Institut Universitaire d'Hématologie, Hôpital Saint Louis , Paris, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Neves
authors.affiliation: Inserm U1173 and University of Versailles Saint-Quentin, Montigny-le-Bretonneux, France; APHP, Ambroise Paré Hospital, Division of Genetics, Boulogne-Billancourt, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Germaud
authors.affiliation: Inserm U1173 and University of Versailles Saint-Quentin, Montigny-le-Bretonneux, France; APHP, Ambroise Paré Hospital, Division of Genetics, Boulogne-Billancourt, France.
authors.forename: Henri Jean
authors.initials: HJ
authors.lastname: Garchon
authors.affiliation: INSERMU1160, Institut Universitaire d'Hématologie, Hôpital Saint Louis , Paris, France.
authors.forename: Wahid
authors.initials: W
authors.lastname: Boukouaci
authors.affiliation: INSERMU1160, Institut Universitaire d'Hématologie, Hôpital Saint Louis , Paris, France.
authors.forename: Ryad
authors.initials: R
authors.lastname: Tamouza
authors.affiliation: APHP, Department of Dermatology, Hospital Cochin, University Paris Descartes , Paris, France.
authors.forename: Johan
authors.initials: J
authors.lastname: Chanal
authors.affiliation: APHP, Department of Dermatology, Hospital Cochin, University Paris Descartes, Paris, France; Université Pierre et Marie Curie, Paris, France.
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Avril
authors.affiliation: INSERMU1160, Institut Universitaire d'Hématologie, Hôpital Saint Louis , Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Toubert
authors.affiliation: U1015 INSERM-CIC, Institut Gustave Roussy, Villejuif, France; University of Paris Sud XI, Kremlin Bicêtre, France; Institut de Cancérologie Gustave Roussy Cancer Campus (GRCC), Villejuif, France; INSERM, U1015, GRCC, Villejuif, France; Center of Clinical Investigations in Biotherapies of Cancer, CICBT507, GRCC, Villejuif, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
authors.affiliation: U1015 INSERM-CIC, Institut Gustave Roussy , Villejuif, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rusakiewicz
authors.affiliation: INSERMU1160, Institut Universitaire d'Hématologie, Hôpital Saint Louis , Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Caignard
keywords: NK receptors; immunogenetics; melanoma; natural Killer cells