NKp46 is a diagnostic biomarker and may be a therapeutic target in gastrointestinal T-cell lymphoproliferative diseases: A CELAC study
| Autor: | Nicolas Guegan, Florence Lhospice, Sascha Cording, Amélie Trinquand, Julie Bruneau, Olivier Hermine, Virginie Verkarre, Nicole Brousse, Christophe Cellier, Georgia Malamut, Elizabeth Macintyre, Felipe Suarez, Laurent Frenzel, Vahid Asnafi, Morgane Cheminant, Sherine Khater, Bertrand Meresse, Ambroise Marçais, Nadine Cerf-Bensussan, Tom van Gils, Chris J. J. Mulder, Thierry Jo Molina, Ludovic Lhermitte, C. cile Bonnafous, David Sibon, Anne-Sophie Jannot, Richard Delarue, Laurent Pouyet |
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| Přispěvatelé: | Gastroenterology and hepatology, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications (ERL 8254 - Equipe Inserm U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Département de Pathologie [CHU Necker], Université Sorbonne Paris Cité (USPC)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), VU University Medical Center [Amsterdam], Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), University Paris Descartes Sorbonne Paris Cité, Imagine Institute, Paris, Mi-mAbs (C/O CIML), Centre d'Immunologie de Marseille - Luminy (CIML), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Innate Pharma, Service de gastroenterologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Mécanismes cellulaires et moléculaires des désordres hématologiques et implications thérapeutiques = Molecular mechanisms of hematological disorders and therapeutic implications (ERL 8254), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male MESH: Biopsy / methods Enteropathy-Associated T-Cell Lymphoma / diagnosis Entropathy-Associated T-Cell Lymphoma / etiology Enteropathy-Associated T-Cell Lymphoma / immunology T cell Biopsy [SDV.CAN]Life Sciences [q-bio]/Cancer Coeliac Disease Coeliac disease 03 medical and health sciences 0302 clinical medicine Enteropathy-Associated T-Cell Lymphoma Intestinal mucosa Intestine Small medicine Cytotoxic T cell Humans Intestinal Mucosa MESH: Enteropathy-Associated T-Cell Lymphoma / pathology Intestinal Mucosa / immunology Intestinal Mucosa / pathology Killer Cells Natural / immunology Antibody Targeted Therapy Cells Cultured business.industry Natural Cytotoxicity Triggering Receptor 1 Gastroenterology MESH: Natural Cytotoxicity Triggering Receptor 1 / immunology Antibodies Monoclonal [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology Middle Aged medicine.disease NKG2D Prognosis 3. Good health Killer Cells Natural Celiac Disease 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer research Intraepithelial lymphocyte Enteropathy-associated T-cell lymphoma Female France Gastrointestinal Lymphoma business Ex vivo Biomarkers Tumour markers |
| Zdroj: | Gut, 68(8), 1396-1405. BMJ Publishing Group Gut Gut, BMJ Publishing Group, 2019, 68 (8), pp.1396-1405. ⟨10.1136/gutjnl-2018-317371⟩ Cheminant, M, Bruneau, J, Malamut, G, Sibon, D, Guegan, N, van Gils, T, Cording, S, Trinquand, A, Verkarre, V, Lhermitte, L, Brousse, N, Jannot, A-S, Khater, S, Frenzel, L, Delarue, R, Suarez, F, Marçais, A, Mulder, C J J, Macintyre, E, Asnafi, V, Pouyet, L, Bonnafous, C C, Lhospice, F, Molina, T J, Meresse, B, Cellier, C, Cerf-Bensussan, N & Hermine, O 2019, ' NKp46 is a diagnostic biomarker and may be a therapeutic target in gastrointestinal T-cell lymphoproliferative diseases: A CELAC study ', Gut, vol. 68, no. 8, pp. 1396-1405 . https://doi.org/10.1136/gutjnl-2018-317371 Gut, 2019, 68 (8), pp.1396-1405. ⟨10.1136/gutjnl-2018-317371⟩ |
| ISSN: | 0017-5749 1468-3288 |
| DOI: | 10.1136/gutjnl-2018-317371⟩ |
| Popis: | ObjectivesPrimary GI T-cell lymphoproliferative diseases (T-LPD) are heterogeneous entities, which raise difficult diagnosis and therapeutic challenges. We have recently provided evidences that lymphomas complicating coeliac disease (CD) arise from innate-like lymphocytes, which may carry NK receptors (NKRs).DesignNKRs expression was compared by flow cytometry in intraepithelial lymphocytes (IEL) from CD, type I or type II refractory CD (RCD). NKp46 was next assessed by immunohistochemistry in paraffin-embedded biopsies from 204 patients with CD, RCDI, RCDII or GI T-cell lymphomas and from a validation cohort of 61 patients. The cytotoxic properties of an anti-NKp46 monoclonal antibody conjugated to pyrrolobenzodiazepine (PBD) was tested ex vivo in human primary tumour cells isolated from fresh duodenal biopsies.ResultsNKp46 (but not CD94, NKG2A, NKG2C, NKG2D) was significantly more expressed by malignant RCDII IEL than by normal IEL in CD and RCDI. In paraffin biopsies, detection of >25 NKp46+ IEL per 100 epithelial cells discriminated RCDII from CD and RCDI. NKp46 was also detected in enteropathy-associated T-cell lymphomas (EATL, 24/29) and in monomorphic epitheliotropic intestinal T-cell lymphomas (MEITL, 4/4) but not in indolent T-LPD (0/15). Treatment with anti-NKp46-PBD could efficiently and selectively kill human NKp46+ primary IEL ex vivo.ConclusionNKp46 is a novel biomarker useful for diagnosis and therapeutic stratification of GI T-LPD. Strong preclinical rationale identifies anti-NKp46-PBD as a promising therapy for RCDII, EATL and MEITL. |
| Databáze: | OpenAIRE |
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