Heterogeneous response patterns of alveolar macrophages from patients withlung cancer by stimulation with interferon-gamma

Background: Macrophages are considered to play an important role in the hos t defense against malignant tumors. In this study, cytotoxic activity of al veolar macrophages (AM) derived from 32 patients with lung cancer was inves tigated. Methods: AM were aseptically obtained by ravage from resected lung and subs equently tested for cytolytic activity against QG56, a lung squamous cell l ine, following treatment with recombinant interferon-gamma (IFN-gamma). Results: in seven patients (21.9%), AM showed no cytotoxicity even though A M were incubated with IFN-gamma. In 20 (62.5%), AM showed substantial cytot oxicity in response to IFN-gamma in a dose-dependent manner. In the other f ive (15.6%), relatively strong cytotoxicity was observed even without prein cubation with IFN-gamma, Such a heterogeneous profile of the cytotoxicity o f AM might be a reflection of various activated states of AM since the pote ntial of cytotoxicity and that of IL-1 secretion were almost parallel. Both IFN-gamma dependent and -independent cytotoxicity were partially blocked e ither by anti-tumor necrosis factor-alpha (TNF-alpha) antibody or by the in hibitor of nitric oxide synthesis. However, those activities were completel y abrogated by both treatments. Since the supernatant of AM culture exhibit ed TNF-alpha-mediated but not NO-mediated cytolysis, TNF-alpha could mediat e a bystander killing whereas NO acts in close contact with tumor cells. Conclusion: The AM have anti-tumor cytotoxicity in lung cancer although the cytolytic potential is heterogeneous and that the tumor lysis by AM is med iated by both TNF-alpha and NO production.