IMPAIRED ACTIVATION OF TUMORICIDAL FUNCTION IN MACROPHAGES FROM MAMMARY-TUMOR BEARERS - THE ROLE OF IFN-GAMMA

The growth of the DI-DMBA-3 mammary adenocarcinoma in BALB/c mice resu lts in a profound deficit in the tumoricidal function of their periton eal elicited macrophages (PEM) after stimulation with lipopolysacchari de (LPS). The capacity of these macrophages to respond to stronger sig nals, such as a combination of LPS and low levels (5 U/ml) of interfer on-gamma (IFN-gamma) is also impaired. Importantly, a combination of h igh levels (50 U/ml) of IFN-gamma with 10 mug/ml of LPS, is able to tr igger a cytolytic response in macrophages from tumor bearing mice agai nst mammary tumor target cells, indicating that their lytic machinery is intact. However, IFN-gamma production is severely diminished in T l ymphocytes from tumor bearing mice as detected by ELISA, moreover, Nor thern blots revealed that the levels of IFN-gamma RNA are also decreas ed in T cells from tumor bearers. The cooperation between T cells and macrophages is mediated, at least in part, by IFN-gamma. Thus, mammary tumors have die potential to overcome host defenses, either by affect ing the capacity of macrophages to respond adequately to activating ag ents, and/or by impairing the production of T-cell derived lymphokines important in macrophage activation for tumor killing.