title: Alternatively spliced NKp30 isoforms affect the prognosis of gastrointestinal stromal tumors.
abstract: The natural killer (NK) cell receptor NKp30 is involved in the recognition of tumor and dendritic cells (DCs). Here we describe the influence of three NKp30 splice variants on the prognosis of gastrointestinal sarcoma (GIST), a malignancy that expresses NKp30 ligands and that is treated with NK-stimulatory KIT tyrosine kinase inhibitors. Healthy individuals and those with GIST show distinct patterns of transcription of functionally different NKp30 isoforms. In a retrospective analysis of 80 individuals with GIST, predominant expression of the immunosuppressive NKp30c isoform (over the immunostimulatory NKp30a and NKp30b isoforms) was associated with reduced survival of subjects, decreased NKp30-dependent tumor necrosis factor-α (TNF-α) and CD107a release, and defective interferon-γ (IFN-γ) and interleukin-12 (IL-12) secretion in the NK-DC cross-talk that could be restored by blocking of IL-10. Preferential NKp30c expression resulted partly from a single-nucleotide polymorphism at position 3790 in the 3' untranslated region of the gene encoding NKp30. The genetically determined NKp30 status predicts the clinical outcomes of individuals with GIST independently from KIT mutation.
authors.affiliation: Institut Gustave Roussy (IGR), Villejuif, France.
authors.forename: Nicolas F
authors.initials: NF
authors.lastname: Delahaye
authors.forename: Sylvie
authors.initials: S
authors.lastname: Rusakiewicz
authors.forename: Isabelle
authors.initials: I
authors.lastname: Martins
authors.forename: Cédric
authors.initials: C
authors.lastname: Ménard
authors.forename: Stephan
authors.initials: S
authors.lastname: Roux
authors.forename: Luc
authors.initials: L
authors.lastname: Lyonnet
authors.forename: Pascale
authors.initials: P
authors.lastname: Paul
authors.forename: Matthieu
authors.initials: M
authors.lastname: Sarabi
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chaput
authors.forename: Michaela
authors.initials: M
authors.lastname: Semeraro
authors.forename: Véronique
authors.initials: V
authors.lastname: Minard-Colin
authors.forename: Vichnou
authors.initials: V
authors.lastname: Poirier-Colame
authors.forename: Kariman
authors.initials: K
authors.lastname: Chaba
authors.forename: Caroline
authors.initials: C
authors.lastname: Flament
authors.forename: Véronique
authors.initials: V
authors.lastname: Baud
authors.forename: Hélène
authors.initials: H
authors.lastname: Authier
authors.forename: Saadia
authors.initials: S
authors.lastname: Kerdine-Römer
authors.forename: Marc
authors.initials: M
authors.lastname: Pallardy
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cremer
authors.forename: Laetitia
authors.initials: L
authors.lastname: Peaudecerf
authors.forename: Bénédita
authors.initials: B
authors.lastname: Rocha
authors.forename: Dominique
authors.initials: D
authors.lastname: Valteau-Couanet
authors.forename: Javier Celis
authors.initials: JC
authors.lastname: Gutierrez
authors.forename: Jacques A
authors.initials: JA
authors.lastname: Nunès
authors.forename: Frédéric
authors.initials: F
authors.lastname: Commo
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bonvalot
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ibrahim
authors.forename: Philippe
authors.initials: P
authors.lastname: Terrier
authors.forename: Paule
authors.initials: P
authors.lastname: Opolon
authors.forename: Cristina
authors.initials: C
authors.lastname: Bottino
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.forename: Jan
authors.initials: J
authors.lastname: Tavernier
authors.forename: Pascal
authors.initials: P
authors.lastname: Rihet
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Coindre
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
authors.forename: Nicolas
authors.initials: N
authors.lastname: Isambert
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Emile
authors.forename: Eric
authors.initials: E
authors.lastname: Vivier
authors.forename: Axel
authors.initials: A
authors.lastname: Lecesne
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
mesh_terms: D017398:Alternative Splicing / Q000235:genetics* / Q000502:physiology; D045744:Cell Line, Tumor; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology; D007694:Killer Cells, Natural / Q000502:physiology; D052118:Lysosomal-Associated Membrane Protein 1 / Q000502:physiology; D055628:Natural Cytotoxicity Triggering Receptor 3 / Q000235:genetics* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011379:Prognosis; D020033:Protein Isoforms; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D052118:Lysosomal-Associated Membrane Protein 1; C431710:NCR3 protein, human; D055628:Natural Cytotoxicity Triggering Receptor 3; D020033:Protein Isoforms; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D007371:Interferon-gamma; D019009:Proto-Oncogene Proteins c-kit