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

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), 500 mu g cytosine phosphate guanosine oligodeoxynucleotide (CpG-ODN) (n = 6), cisplatin-fibrin (n = 6), cisplatin-fibrin + 500 mu g 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 610 mm(3) in the control group to 11.7 mm(3) in the cisplatin-fibrin group (p = 0.004) and to 21.8 mm(3) in the cisplatin-fibrin + CpG group (p = 0.004). Pro-inflammatory cytokines (Interferon-gamma (IFN-gamma), Interleukin-6 (IL-6), Interleukin-12 (IL-12)) were increased after treatment with cisplatin-fibrin + CpG in comparison to cisplatin-fibrin atone 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. (C) 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.