Decrease of Interleukin-2 secretion is a new independent prognostic factor associated with poor survival in patients with small-cell lung cancer

Background: We have previously shown that suppression of Interleukin-2(IL-2) secretion was mediated by transforming growth factor (TGF) 1secreted by small-cell lung cancer (SCLC) tumor cells. We have also shown thatIL-2 secretion was significantly impaired in patients with SCLC at the timeof diagnosis. Reconstitution of cytokine secretion correlated with reductionof tumor load. These data suggested that the immune system was suppressed bythe tumor. To address the clinical relevance of cytokine suppression in SCLC,we investigated the correlation of the level of IL-2 secretion with survival.Patients and methods: The significance of correlations between singleparameters in the test groups was calculated by using the linear regressionanalysis, the Wilcoxon rank sum test and the exact test according to Fisher.Using the Kaplan–Meier method, the log-rank test and the Cox-regressionmodel, we analysed the relation of IL-2 secretion in whole blood cell culturesfrom 52 patients with SCLC at the time of diagnosis to established prognosticfactors relevant for survival in SCLC.Results: Impairment of IL-2 secretion significantly correlates to survivalin SCLC (P = 0.004). Further univariate and multivariate analysis showed thatthis prognostic factor is independent from other factors of prognosticrelevance in SCLC, namely stage of disease, neurone specific enolase (NSE),lactate dehydrogenase (LDH), age, and sex. More important, the prognosticvalue of IL-2 secretion is comparable to the most predominant prognosticfactors for survival in SCLC identified so far. In the final model of the coxregression analysis, the P-value for IL-2 secretion in relation to stage ofdisease was 0.012 and 0.019, respectively.Conclusions: IL-2 secretion at the time of diagnosis represents anindependent prognostic factor for survival in SCLC. Although its prognosticvalue has to be confirmed in a larger group of patients, our resultsdemonstrate that IL-2 secretion may play an important role in diagnosis andtreatment of SCLC. Moreover, in contrast to other prognostic factors,impairment of IL-2 secretion may help to understand immunosuppression in SCLCand, thus, important elements of the pathogenesis of this disease.