Impaired tumoricidal function of alveolar macrophages from patients with non-small cell lung cancer

The capacity of alveolar macrophages and peripheral blood monocytes from patients with non-small cell lung cancer to develop tumoricidal function after in vitro stimulation with different macrophage activators was investigated. Alveolar macrophages were found to be impaired in their ability to develop cytotoxic activity compared with either the peripheral blood monocytes from the same patients or alveolar macrophages from patients with nonmalignant lung disorders. This result was observed consistently under diverse culture conditions and with different macrophage activators including gamma-interferon (gamma-IFN), granulocyte-macrophage colony-stimulating factor (GM-CSF), phorbol myristate acetate, or endotoxin. The impairment in tumoricidal function observed in alveolar macrophages was not associated with reduced target cell binding compared to peripheral blood monocytes. Alveolar macrophages from patients with lung cancer were found to secrete significantly greater amounts of tumor necrosis factor (TNF) and interleukin-1 (IL-1) than either peripheral blood monocytes from the same patients or alveolar macrophages from the patients with nonmalignant disorders. These results are consistent with either different regulatory pathways for cytotoxicity and cytokine secretion in the alveolar macrophages of patients with lung cancer or diversity in the subpopulations of cells responsible for these functions.