Prognostic significance of cytokine modulation in non‐small cell lung cancer

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Abstract
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.

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