Accéder directement au contenu Accéder directement à la navigation
Article dans une revue

Human NK cells activated by EBV + lymphoblastoid cells overcome anti-apoptotic mechanisms of drug resistance in haematological cancer cells

Abstract : Natural killer (NK) cells recognize and eliminate transformed or infected cells that have downregulated MHC class-I and express specific activating ligands. Recent evidence indicates that allogeneic NK cells are useful to eliminate haematological cancer cells independently of MHC-I expression. However, it is unclear if transformed cells expressing mutations that confer anti-apoptotic properties and chemoresistance will be susceptible to NK cells. Allogeneic primary human NK cells were activated using different protocols and prospectively tested for their ability to eliminate diverse mutant haematological and apoptotic-resistant cancer cell lines as well as patient-derived B-cell chronic lymphocytic leukemia cells with chemotherapy multiresistance. Here, we show that human NK cells from healthy donors activated in vitro with Epstein Barr virus positive (EBV C)-lymphoblastoid cells display an enhanced cytotoxic and proliferative potential in comparison to other protocols of activation such a K562 cells plus interleukin (IL)2. This enhancement enables them to kill more efficiently a variety of haematological cancer cell lines, including a panel of transfectants that mimic natural mutations leading to oncogenic transformation and chemoresistance (e.g., overexpression of Bcl-2, Bcl-X L and Mcl-1 or downregulation of p53, Bak/Bax or caspase activity). The effect was also observed against blasts from B-cell chronic lymphocytic leukemia patients showing multi-resistance to chemotherapy. Our findings demonstrate that particular in vitro activated NK cells may overcome anti-apoptotic mechanisms and oncogenic alterations frequently occurring in transformed cells, pointing toward the use of EBV C-lymphoblastoid cells as a desirable strategy to activate NK cells in vitro for the purpose of treating haematological neoplasia with poor prognosis.
Type de document :
Article dans une revue
Liste complète des métadonnées
Contributeur : Alexandre Philips Connectez-vous pour contacter le contributeur
Soumis le : mercredi 3 février 2021 - 10:20:37
Dernière modification le : vendredi 22 octobre 2021 - 14:58:49
Archivage à long terme le : : mardi 4 mai 2021 - 18:28:02


IRMB 4_P38_Human NK cells acti...
Fichiers éditeurs autorisés sur une archive ouverte


Distributed under a Creative Commons Paternité 4.0 International License




Martin Sanchez-Martinez, Gemma Azaceta, Aura Muntasell, Nacho Aguiló, David Nuñez, et al.. Human NK cells activated by EBV + lymphoblastoid cells overcome anti-apoptotic mechanisms of drug resistance in haematological cancer cells. OncoImmunology, Taylor & Francis, 2015, 4 (3), pp.e991613. ⟨10.4161/2162402X.2014.991613⟩. ⟨hal-01835574⟩



Consultations de la notice


Téléchargements de fichiers