Prevention of spontaneous tumors of aged mice by immunopharmacologic manipulation: study of immune antitumor mechanisms.

Effects produced by long-term application of three immune modifiers (azimexon, retinoic acid, and tuftsin) on the depressed immune systems of 18-month-old inbred C57BL/6 female mice were investigated. The effect of each agent was examined on four cell types (cytotoxic T-cells, K-cells, NK cells, and macrophages) possibly involved in antitumor defenses and on the spontaneous tumor development that accompanied advancing age. Three substances chosen for this study appeared able to alter immune parameters, and each one displayed its own pattern of activity. Common to all three agents were an increase of age-depressed tumoricidal activity of peritoneal macrophages and no effect on the depressed NK activity of spleen cells. Retinoic acid increased splenic K-cell activity, already elevated in aged mice and unaffected by the other two agents. Cytotoxic T-cell activity, diminished by age, was stimulated considerably by retinoic acid and by tuftsin but only slightly by azimexon. Histopathologic studies revealed a decrease in the incidence of spontaneous tumors in the 3 treated groups. This decrease was statistically significant in the retinoic acid- and tuftsin-treated groups when compared with the incidence in untreated mice of the same age. Correlation of drug-induced modifications of the immune system with tumor incidence in aged mice was attempted.