Le Maux Chansac B. auteur aut IRD Missé Dorothée auteur aut IRD Richon C. auteur aut IRD Vergnon I. auteur aut IRD Kubin M. auteur aut IRD Soria J. C. auteur aut IRD Moretta A. auteur aut IRD Chouaib S. auteur aut IRD Mami-Chouaib F. auteur aut IRD text journalArticle eng Natural cytotoxicity receptors and NKG2D correspond to major activating receptors involved in triggering of tumor cell lysis by human NK cells. In this report, we investigated the expression of NKG2D ligands (NKG2DLs), MHC class I-related chain (MIC) A, MICB and UL16-binding proteins 1, 2 and 3, on a panel of human non-small-cell lung carcinoma cell lines, and we analyzed their role in tumor cell susceptibility to NK cell lysis. Although adenocarcinoma (ADC) cells expressed heterogeneous levels of NKG2DLs, they were often resistant to NK cell-mediated killing. Resistance of a selected cell line, ADC-Coco, to allogeneic polyclonal NK cells and autologous NK cell clones correlated with shedding of NKG2DLs resulting from a matrix metalloproteinase (MMP) production. Treatment of ADC-Coco cells with a MMP inhibitor (MMPI) combined with IL-15 stimulation of autologous NK cell clones lead to a potentiation of NK cell-mediated cytotoxicity. This lysis is mainly NKG2D mediated, since it is abrogated by anti-NKG2D-neutralizing mAb. These results suggest that MMPIs, in combination with IL-15, may be useful for overcoming tumor cell escape from the innate immune response. specialized Nk cell-activating receptors Nkg2dl Nsclc Tumor-infiltrating nk cells 050 20 7 801-810 2008 0953-8178 https://www.documentation.ird.fr/hor/PAR00002538 10.1093/intimm/dxn038 0953-8178 https://www.documentation.ird.fr/hor/PAR00002538 IRD - Base Horizon / Pleins textes 2008-08-08 2017-08-23 PAR00002538 fre