Abstract
Natural killer (NK) cells are currently used in clinical trials to treat tumors. However, such therapies still suffer from problems such as donor variability, reproducibility, and more, which prevent a wider use of NK cells therapeutics. Here we show a potential immunotherapy combining NK cell-mediated tumor eradiation and long non-coding (lnc) RNAs. We overexpressed the interferon (IFN) γ<math><mrow><mi>γ</mi></mrow></math> secretion-enhancing lncRNA nettoie Salmonella pas Theiler's (NeST) in the NK cell-like cell line YTS. YTS cells express the co-stimulatory receptor 2B4 whose main ligand is CD48. On YTS cells, 2B4 functions by direct activation. We showed that NeST overexpression in YTS cells resulted in increased IFNγ<math><mrow><mi>γ</mi></mrow></math> release upon interaction with CD48 (selectively enhanced (se)YTS cells). Following irradiation, the seYTS cells lost proliferation capacity but were still able to maintain their killing and IFNγ<math><mrow><mi>γ</mi></mrow></math> secretion capacities. Finally, we demonstrated that irradiated seYTS inhibit tumor growth in vivo. Thus, we propose seYTS cells as off-the-shelve therapy for CD48-expressing tumors.