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Immuno-chemotherapy reduces recurrence of malignant pleural mesothelioma: an experimental setting

Ampollini, Luca ; Soltermann, Alex ; Felley-Bosco, Emanuela ; Lardinois, Didier ; Arni, Stephan ; Speck, Roberto F. ; Weder, Walter ; Opitz, Isabelle

In: European Journal of Cardio-Thoracic Surgery, 2009, vol. 35, no. 3, p. 457-462

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    Titre
    • Immuno-chemotherapy reduces recurrence of malignant pleural mesothelioma: an experimental setting
    Auteur
    • Ampollini, Luca. Thoracic Surgery, University Hospital of Zurich, Switzerland
    • Soltermann, Alex. Department of Pathology, Zurich, Switzerland
    • Felley-Bosco, Emanuela. Laboratory of Molecular Oncology, Zurich, Switzerland
    • Lardinois, Didier. Thoracic Surgery, University Hospital of Zurich, Switzerland
    • Arni, Stephan. Thoracic Surgery, University Hospital of Zurich, Switzerland
    • Speck, Roberto F.. Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, Switzerland
    • Weder, Walter. Thoracic Surgery, University Hospital of Zurich, Switzerland
    • Opitz, Isabelle. Thoracic Surgery, University Hospital of Zurich, Switzerland
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • European Journal of Cardio-Thoracic Surgery, 2009, vol. 35, no. 3, p. 457-462. Elsevier Science B.V.
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:296421
    Summary
    Objective: To assess the effect of immuno-chemotherapy on the extent of local tumour recurrence in an established rat model of malignant pleural mesothelioma (MPM). Methods: Six days after subpleural inoculation of a syngeneic MPM cell line Interleukin-45 (IL-45), left-sided pneumonectomy and resection of the tumour nodule was performed. Animals were randomised into four treatment groups for intrapleural therapy: control (n=6), 500μg cytosine phosphate guanosine oligodeoxynucleotide (CpG-ODN) (n=6), cisplatin-fibrin (n=6), cisplatin-fibrin+500μg CpG (n=6). Six days later the volume of tumour recurrence was assessed, which was the primary endpoint. Secondary endpoints were quantification of the ratio host/tumour cells in the local recurrence and cytokine expression profile in the tumour tissue by real time quantitative PCR (qPCR). T lymphocyte subpopulations in the tumour recurrence tissue were evaluated by immunohistochemistry. Treatment-related toxicity was monitored by measuring blood chemistry and complete blood count. Results: The volume of tumour recurrence was significantly reduced from 610mm3 in the control group to 11.7mm3 in the cisplatin-fibrin group (p=0.004) and to 21.8mm3 in the cisplatin-fibrin+CpG group (p=0.004). Pro-inflammatory cytokines (Interferon-γ (IFN-γ), Interleukin-6 (IL-6), Interleukin-12 (IL-12)) were increased after treatment with cisplatin-fibrin+CpG in comparison to cisplatin-fibrin alone but differences were not statistically significant. We found a higher ratio of host/tumour cells in the cisplatin-fibrin+CpG group (45/55%) compared to the cisplatin-fibrin group (27/73%). In comparison to the control group, animals treated with cisplatin-fibrin+CpG showed a higher number of CD8+ T-cells in the tumour tissue. No significant treatment-related toxicity was observed. Conclusions: Adjuvant treatment with chemotherapy or immuno-chemotherapy leads to significant reduction of mesothelioma recurrence after surgery in this rat MPM model. Immuno-chemotherapy resulted in an increased recruitment of inflammatory cells to the site of tumourigenesis and elicited higher level of tumour growth inhibiting cytokines