Whether or not cytokine secretion is impaired in patients with small-cell lung cancer (SCLC), is unknown. We therefore investigated whether cytokine secretion by immunocompetent cells may be suppressed in patients with SCLC

We determined cytokine secretion by lymphocytes and monocytes in whole blood cell cultures from 58 patients with SCLC, 95 patients with non-small-cell lung cancer (NSCLC), 10 patients with nonmalignant lung disease and from 44 normal healthy individuals by using an enzyme-linked immunosorbent assay (ELISA) specific for the different cytokines measured.

Compared to normal controls, immunocompetent cells from patients with SCLC secreted significantly lower amounts of IL-2, IFN α, and IFN γ upon mitogen stimulation. TNF α-secretion was significantly reduced in SCLC extensive disease but not in SCLC limited disease. In contrast, secretion of IL-1 α and IL-1 β was not reduced. In patients with NSCLC, secretion of IL-2 and IFN α was significantly reduced. Reduction of IFN γ secretion was significant in metastasized NSCLC and marginally significant in localized NSCLC. Secretion of TNF α, IL-1 α and IL-1 β was not impaired. In addition, cytokine secretion in SCLC patients substantially improved upon successful reduction of tumor load by chemotherapy but not upon ineffective chemotherapy. Furthermore, TGF β₁, suppressed secretion of IL-2, IFN α, IFN γ, TNF α, but not of IL-lα and IL-1 β in whole blood cell cultures from healthy individuals.

Suppression of cytokine secretion in patients with SCLC was selective, dependent on tumor 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 β₁, secreted by SCLC cell lines induced the same selective cytokine suppression as that found in SCLC patients. However, whether or not tumor-derived TGF β₁, is a factor inducing selective immunosuppression in SCLC patients is presently unclear.