SELECTIVE SUPPRESSION OF CYTOKINE SECRETION IN PATIENTS WITH SMALL-CELL LUNG-CANCER

Background: Whether or not cytokine secretion is impaired in patients with small-cell lung cancer (SCLC), is unknown. We therefore investiga ted whether cytokine secretion by immunocompetent cells may be suppres sed in patients with SCLC. Patients and methods: We determined cytokin e secretion by lymphocytes and monocytes in whole blood cell cultures from 58 patients with SCLC, 95 patients with non-small-cell lung cance r (NSCLC), 10 patients with nonmalignant lung disease and from 44 norm al healthy individuals by using an enzyme-linked immunosorbent assay ( ELISA) specific for the different cytokines measured. Results: Compare d to normal controls, immunocompetent cells from patients with SCLC se creted significantly lower amounts of IL-2, IFN alpha, and IFN gamma u pon mitogen stimulation. TNF alpha-secretion was significantly reduced in SCLC extensive disease but not in SCLC limited disease. In contras t, secretion of IL-1 alpha and IL-1 beta was nor reduced. In patients with NSCLC, secretion of IL-2 and IFN alpha was significantly reduced. Reduction of IFN gamma secretion was significant in metastasized NSCL C and marginally significant in localized NSCLC. Secretion of TNF alph a, IL-1 alpha and IL-1 beta was not impaired. In addition, cytokine se cretion in SCLC patients substantially improved upon successful reduct ion of tumor load by chemotherapy but not upon ineffective chemotherap y. Furthermore, TGF beta(1), suppressed secretion of IL-2, IFN alpha, IFN gamma,TNF alpha, but not of IL-1 alpha and IL-1 beta in whole bloo d cell cultures from healthy individuals. Conclusions: Suppression of cytokine secretion in patients with SCLC was selective, dependent on t umor load, different from immunosuppression in NSCLC and seemed to be reconstituted upon reduction of tumor load. These results may suggest interactions between tumor cells and the immune system. TGF beta(1), s ecreted by SCLC cell lines induced the same selective cytokine suppres sion as that found in SCLC patients. However, whether or not tumor-der ived TGF beta(1), is a factor inducing selective immunosuppression in SCLC patients is presently unclear.