Title :

NKp46 is a diagnostic biomarker and may be a therapeutic target in gastrointestinal T-cell lymphoproliferative diseases: a CELAC study.

Author(s) :

Cheminant, Morgane [Auteur]
Bruneau, Julie [Auteur]
Malamut, Georgia [Auteur]
Sibon, David [Auteur]
Guegan, Nicolas [Auteur]
Van Gils, Tom [Auteur]
Cording, Sascha [Auteur]
Trinquand, Amelie [Auteur]
Verkarre, Virginie [Auteur]
Lhermitte, Ludovic [Auteur]
Brousse, Nicole [Auteur]
Jannot, Anne-Sophie [Auteur]
Khater, Sherine [Auteur]
Frenzel, Laurent [Auteur]
Delarue, Richard [Auteur]
Suarez, Felipe [Auteur]
Marcais, Ambroise [Auteur]
Mulder Chris, J [Auteur]
Macintyre, Elizabeth [Auteur]
Asnafi, Vahid [Auteur]
Pouyet, Laurent [Auteur]
Bonnafous, Cecile [Auteur]
Lhospice, Florence [Auteur]
Molina Thierry, Jo [Auteur]
Meresse, Bertrand [Auteur]
Lille Inflammation Research International Center - U 995 [LIRIC]
Cellier, Christophe [Auteur]
Cerf-Bensussan, Nadine [Auteur]
Hermine, Olivier [Auteur]

Journal title :

Gut

Abbreviated title :

Gut

Publication date :

2018-11-17

ISSN :

1468-3288
1468-3288

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

OBJECTIVES: Primary 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 ...
Show more >OBJECTIVES: Primary 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). DESIGN: NKRs 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. RESULTS: NKp46 (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. CONCLUSION: NKp46 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.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Inserm
Université de Lille
CHU Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286

Research team(s) :

Inflammatory digestive disease : pathophysiology and therapeutic targets developement

Submission date :

2019-03-01T14:07:47Z