Cheminant M, et al. - In view of the recent evidence suggesting the origin of lymphomas complicating coeliac disease (CD) from innate-like lymphocytes, which may carry NK receptors (NKRs), researchers used flow cytometry and compared NKRs expression in intraepithelial lymphocytes (IEL) from CD, type I or type II refractory CD (RCD). They found that malignant RCDII IEL vs normal IEL in CD and RCDI expressed NKp46 (but not CD94, NKG2A, NKG2C, NKG2D) significantly more. In paraffin biopsies, RCDII was differentiated from CD and RCDI by the detection of >25 NKp46+ IEL per 100 epithelial cells. Findings also revealed an efficient and selective killing of human NKp46+ primary IEL ex vivo by anti-NKp46-pyrrolobenzodiazepine (PBD) treatment. Findings revealed the utility of NKp46, as a novel biomarker, for diagnosis and therapeutic stratification of GI T-cell lymphoproliferative diseases. For RCDII, enteropathy-associated T-cell lymphomas and monomorphic epitheliotropic intestinal T-cell lymphomas, anti-NKp46-PBD was discovered as a promising treatment by strong preclinical rationale.