Rusakiewicz, Sylvie, Perier, Aurelie, Semeraro, Michaela, Pitt, Jonathan M., von Strandmann, Elke Pogge, Reiners, Katrin S., Aspeslagh, Sandrine, Piperoglou, Christelle, Vely, Frederic, Ivagnes, Alexandre, Jegou, Sarah, Halama, Niels, Chaigneau, Loic, Validire, Pierre, Christidis, Christos, Perniceni, Thierry, Landi, Bruno, Berger, Anne, Isambert, Nicolas, Domont, Julien, Bonvalot, Sylvie, Terrier, Philippe, Adam, Julien, Coindre, Jean-Michel, Emile, Jean-Francois, Poirier-Colame, Vichnou, Chaba, Kariman, Rocha, Benedita, Caignard, Anne ORCID: 0000-0001-9923-6045, Toubert, Antoine, Enot, David, Koch, Joachim, Marabelle, Aurelien, Lambert, Marion, Caillat-Zucman, Sophie ORCID: 0000-0002-4535-3550, Leyvraz, Serge, Auclair, Christian, Vivier, Eric ORCID: 0000-0001-7022-8287, Eggermont, Alexander, Borg, Christophe, Blay, Jean-Yves ORCID: 0000-0001-7190-120X, Le Cesne, Axel, Mir, Olivier ORCID: 0000-0002-6761-4002 and Zitvogel, Laurence (2017). NKp30 isoforms and NKp30 ligands are predictive biomarkers of response to imatinib mesylate in metastatic GIST patients. OncoImmunology, 6 (1). PHILADELPHIA: TAYLOR & FRANCIS INC. ISSN 2162-402X

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Abstract

Despite effective targeted therapy acting on KIT and PDGFRA tyrosine kinases, gastrointestinal stromal tumors (GIST) escape treatment by acquiring mutations conveying resistance to imatinib mesylate (IM). Following the identification of NKp30-based immunosurveillance of GIST and the off-target effects of IM on NK cell functions, we investigated the predictive value of NKp30 isoforms and NKp30 soluble ligands in blood for the clinical response to IM. The relative expression and the proportions of NKp30 isoforms markedly impacted both event-free and overall survival, in two independent cohorts of metastatic GIST. Phenotypes based on disbalanced NKp30B/NKp30C ratio (Delta BClow) and low expression levels of NKp30A were identified in one third of patients with dismal prognosis across molecular subtypes. This Delta BClow blood phenotype was associated with a pro-inflammatory and immunosuppressive tumor microenvironment. In addition, detectable levels of the NKp30 ligand sB7-H6 predicted a worse prognosis in metastatic GIST. Soluble BAG6, an alternate ligand for NKp30 was associated with low NKp30 transcription and had additional predictive value in GIST patients with high NKp30 expression. Such GIST microenvironments could be rescued by therapy based on rIFN-alpha and anti-TRAIL mAb which reinstated innate immunity.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Rusakiewicz, SylvieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perier, AurelieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Semeraro, MichaelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pitt, Jonathan M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Strandmann, Elke PoggeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reiners, Katrin S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aspeslagh, SandrineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Piperoglou, ChristelleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vely, FredericUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ivagnes, AlexandreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jegou, SarahUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Halama, NielsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chaigneau, LoicUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Validire, PierreUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Christidis, ChristosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Perniceni, ThierryUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Landi, BrunoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Berger, AnneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Isambert, NicolasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Domont, JulienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bonvalot, SylvieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Terrier, PhilippeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Adam, JulienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Coindre, Jean-MichelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Emile, Jean-FrancoisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Poirier-Colame, VichnouUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chaba, KarimanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rocha, BeneditaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caignard, AnneUNSPECIFIEDorcid.org/0000-0001-9923-6045UNSPECIFIED
Toubert, AntoineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Enot, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Koch, JoachimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marabelle, AurelienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lambert, MarionUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Caillat-Zucman, SophieUNSPECIFIEDorcid.org/0000-0002-4535-3550UNSPECIFIED
Leyvraz, SergeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Auclair, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vivier, EricUNSPECIFIEDorcid.org/0000-0001-7022-8287UNSPECIFIED
Eggermont, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borg, ChristopheUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Blay, Jean-YvesUNSPECIFIEDorcid.org/0000-0001-7190-120XUNSPECIFIED
Le Cesne, AxelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mir, OlivierUNSPECIFIEDorcid.org/0000-0002-6761-4002UNSPECIFIED
Zitvogel, LaurenceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-243877
DOI: 10.1080/2162402X.2015.1137418
Journal or Publication Title: OncoImmunology
Volume: 6
Number: 1
Date: 2017
Publisher: TAYLOR & FRANCIS INC
Place of Publication: PHILADELPHIA
ISSN: 2162-402X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GASTROINTESTINAL STROMAL TUMORS; NATURAL-KILLER-CELLS; ANTITUMOR IMMUNITY; CANCER PATIENTS; LUNG-CARCINOMA; C-KIT; ORIGIN; INFILTRATION; INHIBITORS; EFFICACYMultiple languages
Oncology; ImmunologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/24387

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