Assessment of interferon-γ in pleural fluid as a prognostic factor of survival in malignant pleural mesothelioma

Backgound Literature reports suggest that the host immune system may control Malignant Pleural Mesothelioma (MPM) growth, although its activity is limited by regulatory mechanisms. In this retrospective study, we analyzed the levels of pro-inflammatory (IL-1, IL-6, TNF), immune-regulatory (IL-10) and Th1/CTL-related cytokines (IL-12p70, IFN-gamma) in the pleural exudate and their relationship with overall survival (OS) in MPM. Methods Cytokines were quantified by multiplexed immunoassay. Concentrations were dichotomized with respect to the median value. Correlation between cytokine level and OS was assessed using univariate (Kaplan-Meier curves) and multivariate (Cox regression) analyses. Results Regarding outcome, tumor histology, therapies undergone and IFN-gamma were independent prognostic factors of OS in a 72 MPM training cohort. Notably, high concentrations of IFN-gamma halved death probability (HR of high vs low IFN-gamma concentration = 0.491, 95%CI 0.3-0.8, p = 0.007). Also in patients with epithelioid histology and those receiving at least one line of therapy, high IFN-gamma level was an independent factor predictive of OS (HR of high vs low IFN-gamma concentration were 0.497, p = 0.007 and 0.324, p = 0.006, respectively). However, these data were not confirmed in a 77 MPM validation cohort, possibly due to the low IFN-gamma levels encountered in this population, and the heterogeneous distribution of disease stages between the training and the validation cohorts. None of the other cytokines showed any effect on survival. Conclusions High level of IFN-gamma in pleural effusion may be associated with better survival in MPM patients and potentially serve as a prognostic biomarker. Larger prospective studies are needed to ascertain this hypothesis.