Heterogeneous response patterns of alveolar macrophages from patients with lung cancer by stimulation with interferon-γ

Background: Macrophages are considered to play an important role in the host defense against malignant tumors. In this study, cytotoxic activity of alveolar macrophages (AM) derived from 32 patients with lung cancer was investigated. Methods: AM were aseptically obtained by ravage from resected lung and subsequently tested for cytolytic activity against QG56, a lung squamous cell line, following treatment with recombinant interferon-gamma (IFN-gamma). Results: in seven patients (21.9%), AM showed no cytotoxicity even though AM were incubated with IFN-gamma. In 20 (62.5%), AM showed substantial cytotoxicity in response to IFN-gamma in a dose-dependent manner. In the other five (15.6%), relatively strong cytotoxicity was observed even without preincubation with IFN-gamma, Such a heterogeneous profile of the cytotoxicity of AM might be a reflection of various activated states of AM since the potential of cytotoxicity and that of IL-1 secretion were almost parallel. Both IFN-gamma dependent and -independent cytotoxicity were partially blocked either by anti-tumor necrosis factor-alpha (TNF-alpha) antibody or by the inhibitor of nitric oxide synthesis. However, those activities were completely abrogated by both treatments. Since the supernatant of AM culture exhibited TNF-alpha-mediated but not NO-mediated cytolysis, TNF-alpha could mediate 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 mediated by both TNF-alpha and NO production.