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

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Abstract

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.

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Acknowledgments

The study received the financial support from the Kapodistrian National Medical University of Athens, Laiko General Hospital, Agios Thomas 17, 11527, Athens, Greece.

Conflict of interest

None.

Ethical standards

The study was firstly approved by the ethics committee of the National Medical University of Athens, in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All persons gave their informed consent prior to their inclusion in the study.

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Authors and Affiliations

  1. Oncology Unit, Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Agios Thomas 17, 11527, Athens, Greece

    Nikolaos Koufos, Despina Michailidou & Nikolaos Tsavaris

  2. Imperial Clinical Trials Unit-Cancer, Department of Surgery and Cancer, Charing Cross Hospital, Imperial College London, Fulham Palace Rd, London, W6 8RF, UK

    Ioannis D. Xynos

  3. Second Department of Propedeutic Surgery, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, Agios Thomas 17, 11527, Athens, Greece

    Periclis Tomos

  4. Department of Thoracic Surgery, Evaggelismos Hospital, Ipsilantou 45-47, 10676, Athens, Greece

    Kalliopi Athanasiadou

  5. Department of Medicine, 2nd Division of Medical Oncology, Metaxa Cancer Hospital, Mpotasi 51, 18537, Piraeus, Greece

    Christos Kosmas

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  1. Nikolaos Koufos
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Correspondence to Nikolaos Tsavaris.

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Koufos, N., Michailidou, D., Xynos, I.D. et al. Modulation of peripheral immune responses by paclitaxel–ifosfamide–cisplatin chemotherapy in advanced non-small-cell lung cancer. J Cancer Res Clin Oncol 139, 1995–2003 (2013). https://doi.org/10.1007/s00432-013-1514-1

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