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