Effect of nuclear factor κB inhibition on tumor cell sensitivity to natural killer‐mediated cytolytic function

• Published in: European journal of immunology 2001-02, Vol.31 (2), p.433-439
• Main Authors: Mami‐Chouaib, Fathia, Ameyar, Maya, Dorothée, Guillaume, Bentires‐Alj, Mohamed, Dziembowska, Magdalena, Delhalle, Silvie, Gay, Françoise, Stancou, Rodica, Bours, Vincent, Chouaib, Salem
• Format: Article
• Language: English
• Subjects: Cytotoxicity; Human NK cell; NF-^KB protein; NF‐κB
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/1521-4141(200102)31:2<433::AID-IMMU433>3.0.CO;2-T

Inhibition of the transcription factor NF‐κB has been reported to increase cell sensitivity to TNF and some cytotoxic drugs. We investigated the effect of NK‐κB inhibition on the susceptibility of tumor cells to freshly isolated, nonactivated, human NK cells and to a TCRγ / δ T cell clone displaying an MHC‐unrestricted "NK‐like" lysis. Using electrophoretic mobility shift assay, we first demonstrated that NF‐κB / DNA binding activity was induced in target cells following coculture with NK cells or TCRγ / δ T cell clone. To investigate the effect of target cell NF‐κB inhibition on NK‐mediated lysis, we blocked NF‐κB translocation by introducing a human cDNA coding for a mutated IκB‐α. Interestingly, our results indicated that inhibition of NF‐κB did not induce any increase in either granzyme‐dependent non‐MHC‐restricted cytotoxicity mediated by fresh non‐stimulated NK cells and by TCR γ / δ T cell clone or in CD95‐mediated lysis. These results emphasize that NF‐κB expressed in target cells does not play a role in the molecular process related to the control of target cell susceptibility to NK‐mediated lysis and suggest that the NF‐κB pathway is not a general mechanism for controlling the cytotoxic response.