Impaired activation of tumoricidal function in macrophages from mammary tumor bearers: The role of IFN-γ

The growth of the D1-DMBA-3 mammary adenocarcinoma in BALB/c mice results in a profound deficit in the tumoricidal function of their peritoneal elicited macrophages (PEM) after stimulation with lipopolysaccharide (LPS). The capacity of these macrophages to respond to stronger signals, such as a combination of LPS and low levels (5 U/ml) of interferon-gamma (IFN-γ) is also impaired. Importantly, a combination of high levels (50 U/ml) of IFN-γ with 10 μg/ml of LPS, is able to trigger a cytolytic response in macrophages from tumor bearing mice against mammary tumor target cells, indicating that their lytic machinery is intact. However, IFN-γ production is severely diminished in T lymphocytes from tumor bearing mice as detected by ELISA, moreover, Northern blots revealed that the levels of IFN-γ RNA are also decreased in T cells from tumor bearers. The cooperation between T cells and macrophages is mediated, at least in part, by IFN-γ. Thus, mammary tumors have the potential to overcome host defenses, either by affecting the capacity of macrophages to respond adequately to activating agents, and/or by impairing the production of T-cell derived lymphokines important in macrophage activation for tumor killing.