Modulation of peripheral immune responses by paclitaxel–ifosfamide–cisplatin chemotherapy in advanced non-small-cell lung cancer

Purpose The aim of this study was to assess systemic immunological responses in non-small-cell lung cancer (NSCLC) patients with stage III/IV disease during treatment with paclitaxel–ifosfamide–cisplatin (TIP) chemotherapy. Methods Peripheral blood mononuclear cells (PBMCs) collected from healthy donors (HD) ( n = 20) and chemotherapy-naive NSCLC patients treated with TIP ( n = 32) were tested for production of IL-1, TNF-α, TNF-β, IL-6, IL-8, IL-10, IL-12 and IL-2 upon polyclonal stimulation with anti-CD3 mAb. They were further assessed over a treatment period of twelve weeks (i.e., four treatment cycles). Results PBMCs from NSCLC patients produced higher IL-1, TNF-α, TNF-β, IL-6, IL-8, IL-10 and IL-12 levels, whereas IL-2 exhibited lower values compared to HD ( p < 0.001 for all parameters). Of interest, patients who responded to treatment had significantly higher increases in IL-2 ( p < 0.001) and significantly higher decreases in IL-1 ( p < 0.001), TNF-α ( p < 0.001), TNF-β ( p < 0.001), IL-6 ( p = 0.02), IL-8 ( p < 0.001), IL-10 ( p < 0.001) and IL-12 ( p < 0.001) levels. Non-responders revealed post-therapeutically a significantly higher increase in IL-1, TNF-α, TNF-β, IL-6, IL-8, IL-10 and IL-12 secretion and a significantly higher decrease in IL-2 levels ( p < 0.001 for all parameters). Patients who responded to treatment and had a significantly higher increase in IL-2 showed a significantly longer median survival ( p value < 0.001, 26 vs. 7.5 months). Conclusion Our study indicates that monitoring cytokine dynamics in patients with advanced NSCLC and especially those of IL-2 in peripheral blood components in vitro could be used as a predictor of treatment-related outcome and overall survival in NSCLC.