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) bet a 1 secreted by small-cell lung cancer (SCLC) tumor cells. We have als o shown that IL-2 secretion was significantly impaired in patients wit h 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 re levance of cytokine suppression in SCLC, we investigated the correlati on of the level of IL-2 secretion with survival. Patients and methods: The significance of correlations between single parameters in the tes t groups was calculated by using the linear regression analysis, the W ilcoxon rank sum test and the exact test according to Fisher. Using th e Kaplan-Meier method, the log-rank lest and the Cox-regression model, we analysed the relation of IL-2 secretion in whole blood cell cultur es from 52 patients with SCLC at the time of diagnosis to established prognostic factors relevant for survival in SCLC. Results: Impairment of IL-2 secretion significantly correlates to survival in SCLC (P = 0. 004). Further univariate and multivariate analysis showed that this pr ognostic factor is independent from other factors of prognostic releva nce in SCLC, namely stage of disease, neurone specific enolase (NSE), lactate dehydrogenase (LDH), age, and sex. More important, the prognos tic value of IL-2 secretion is comparable to the most predominant prog nostic factors for survival in SCLC identified so far. In the final mo del 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. Conclu sions: IL-2 secretion al the time of diagnosis represents an independe nt prognostic factor for survival in SCLC. Although its prognostic val ue has to be confirmed in a larger group Of patients, our results demo nstrate that IL-2 secretion may play an important role in diagnosis an d treatment of SCLC. Moreover, in contrast to other prognostic factors , impairment of IL-2 secretion may help to understand immunosuppressio n in SCLC and, thus, important elements of the pathogenesis of this di sease.