Cytokine secretion: clinical relevance of immunosuppression in non-small cell lung cancer.
Increased production of immunosuppressive IL-10 by non-small cell lung cancer (NSCLC) and increased plasma IL-10 concentrations in NSCLC-patients have recently been correlated to reduced survival. We earlier demonstrated suppression of IL-2 secretion in NSCLC-patients. We now analyzed the influence of IL-2 suppression on survival in NSCLC-patients and influence of IL-10 on IL-2 secretion. The correlation of the IL-2-concentration in whole blood cell cultures from 90 NSCLC-patients at the time of diagnosis to survival was analyzed by using crit-level, the Kaplan-Meier method and the log-rank test. IL-2 secretion capacity at the time of diagnosis significantly influenced survival in NSCLC-patients. With a cut-off value for IL-2 of 1100 pg/ml, the difference in survival was significant with a P-value of 0.014 in the whole patient group. In the subgroup of surgically treated patients (n=33), survival was different with a P-value of 0.011. Moreover, secretion of IL-2 was inhibited in a dose-dependent manner upon addition of IL-10 in whole blood cell cultures from normal individuals. Thus, suppression of IL-2 secretion is predictive for survival of NSCLC-patients and may be mediated by tumor-derived IL-10.
Neuner
A
A
Immunology-Molecular Biology Laboratory, Department of Medical Oncology, Thoraxklinik-Heidelberg gGmbH, Amalienstrasse 5, D-69126, Heidelberg, Germany.
Schindel
M
M
Wildenberg
U
U
Muley
T
T
Lahm
H
H
Fischer
J R
JR
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D008175:Lung Neoplasms / Q000276:immunology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D016753:Interleukin-10