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 investigated whether cytokine secretion by immunocompetent cells may be suppressed in patients with SCLC.


METHODS
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.


RESULTS
Compares to normal controls, immunocompetent cells from patients with SCLC secreted significantly lower amounts of IL-2, IFN alpha, and IFN gamma upon mitogen stimulation. TNF alpha-secretion was significantly reduced in SCLC extensive disease but not in SCLC limited disease. In contrast, secretion of IL-1 alpha and IL-1 beta was not reduced. In patients with NSCLC, secretion of IL-2 and IFN alpha was significantly reduced. Reduction of IFN gamma secretion was significant in metastasized NSCLC and marginally significant in localized NSCLC. Secretion of TNF alpha, IL-1 alpha and IL-1 beta 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 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 blood cell cultures from healthy individuals.


CONCLUSIONS
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 beta 1 secreted by SCLC cell lines induced the same selective cytokine suppression as that found in SCLC patients. However, whether or not tumor-derived TGF beta 1 is a factor inducing selective immunosuppression in SCLC patients is presently unclear.
Fischer
J R
JR
Thorax-Klinik der LVA Baden, Department of Medical Oncology, Heidelberg-Rohrbach, Germany.
Schindel
M
M
Stein
N
N
Lahm
H
H
Gallati
H
H
Krammer
P H
PH
Drings
P
P
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D018288:Carcinoma, Small Cell / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D016207:Cytokines / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016898:Interferon-alpha / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D007371:Interferon-gamma / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D007375:Interleukin-1 / Q000097:blood / Q000378:metabolism; D007376:Interleukin-2 / Q000097:blood / Q000378:metabolism; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D008875:Middle Aged; D012016:Reference Values; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*
D016207:Cytokines; D016898:Interferon-alpha; D007375:Interleukin-1; D007376:Interleukin-2; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma