Analysis of natural killer cell cytotoxicity of cancer patients treated with recombinant interferon

Peripheral blood natural killer (NK) cell cytotoxicity of 24 cancer patients was studied prior to and after single and multiple injections of various doses of human leukocyte recombinant interferon-alpha clone A (IFN-alpha rA). The NK cell cytotoxicity of all cancer patients declined consistently 4 and 8 hours after a single injection of IFN-alpha rA. Twenty-four hours after the injection of IFN-alpha rA, NK cell cytotoxicity of patients with low NK cell phenotype (NK-LR) was significantly augmented, whereas that of patients with medium (NK-MR) or high (NK-HR) NK phenotype was depressed. After multiple injections of IFN-alpha rA, depression of NK cell cytotoxicity was observed in a number of NK-MR and NK-HR patients, but in some patients with NK-LR phenotype, further potentiation was observed. No direct correlation between the NK cell augmentation and serum IFN levels was detected. In in vitro studies, IFN-alpha rA, when added to cultures of target and effector cells of normal individuals in a dose of 10(3) U/ml, was efficient in augmenting NK cell cytotoxicity. NK cell cytotoxicity of cancer patients could also be augmented by the IFN-alpha rA preparation; however, this augmentation occurred only prior to in vivo IFN-alpha rA therapy. After IFN-alpha rA in vivo therapy, their NK cells became refractory to further in vitro IFN-alpha rA treatment.