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

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 introducting 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.