Prognostic significance of cytokine modulation in non-small cell lung cancer.
Increased production of immunosuppressive interleukin-10 (IL-10) by non-small cell lung cancer (NSCLC) and increased serum IL-10 concentrations in NSCLC-patients have recently been correlated to reduced survival. We earlier demonstrated suppression of IL-2 secretion in whole blood cell cultures of NSCLC-patients. We now analyzed the influence of IL-2 secretion on survival in NSCLC-patients and the influence of IL-10 on IL-2 secretion. The correlation of the IL-2 producing ability of whole blood cells in response to PHA in 90 NSCLC-patients at the time of diagnosis to survival was calculated by Crit-level, the Kaplan-Meier method and the log-rank test. With a cut-off value of IL-2 production of 1,100 pg/ml by whole blood cells the difference in survival was significant with a p-value of 0.014. In the group with high and low IL-2, median survival was 14.1 and 9.7 months, respectively. In the subgroup of 33 surgically-treated patients the difference in survival was significant with a p-value of 0.011. In 14 patients with surgical resection of the tumor and high IL-2 at diagnosis and 19 patients with surgical resection, but low IL-2 at diagnosis, median survival was 86.2 and 11.3 months, respectively. Secretion of IL-2 in whole blood cell cultures from healthy individuals was inhibited in a dose-dependent manner upon addition of IL-10. Taken together, suppression of IL-2 secretion has prognostic significance for survival of NSCLC-patients and may be mediated by tumor-derived IL-10.
Neuner
A
A
Immunology-Molecular Biology Laboratory, Thoraxklinik-Heidelberg gGmbH, 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 / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000502:physiology; D007376:Interleukin-2 / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010835:Phytohemagglutinins / Q000494:pharmacology; D011379:Prognosis; D015996:Survival Rate
D014408:Biomarkers, Tumor; D007376:Interleukin-2; D010835:Phytohemagglutinins; D016753:Interleukin-10