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Updated: Jun 26, 2026
Orthotopic Implantation and Peripheral Immune Cell Monitoring in the II-45 Syngeneic Rat Mesothelioma Model
Published on: October 2, 2015
Immuno-chemotherapy reduces recurrence of malignant pleural mesothelioma: an experimental setting
Luca Ampollini1, Alex Soltermann, Emanuela Felley-Bosco
1Thoracic Surgery, University Hospital of Zurich, Switzerland.
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 microg cytosine phosphate guanosine oligodeoxynucleotide (CpG-ODN) (n=6), cisplatin-fibrin (n=6), cisplatin-fibrin+500 microg 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 21.8mm(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 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.
Insights
Adjuvant chemotherapy and immuno-chemotherapy significantly reduced malignant pleural mesothelioma (MPM) recurrence in a rat model. Immuno-chemotherapy enhanced inflammatory cell recruitment and tumor-inhibiting cytokines, showing promise for MPM treatment.
Area of Science:
- Oncology
- Immunology
- Thoracic Surgery
Background:
- Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited treatment options.
- Local tumor recurrence after surgical resection remains a significant clinical challenge.
- Novel therapeutic strategies are needed to improve outcomes for MPM patients.
Purpose of the Study:
- To evaluate the efficacy of immuno-chemotherapy in reducing local tumor recurrence of MPM.
- To assess the impact of treatment on the tumor microenvironment and immune cell infiltration.
- To investigate the safety profile of the therapeutic interventions.
Main Methods:
- A syngeneic rat model of MPM was established via subpleural inoculation of IL-45 cells.
- Following tumor resection, animals received intrapleural therapy: control, CpG-oligodeoxynucleotide (CpG-ODN), cisplatin-fibrin, or cisplatin-fibrin + CpG-ODN.
- Tumor recurrence volume, host/tumor cell ratio, cytokine expression, and T lymphocyte subpopulations were analyzed.
Main Results:
- Cisplatin-fibrin and cisplatin-fibrin + CpG-ODN treatments significantly reduced tumor recurrence volume compared to controls.
- Immuno-chemotherapy (cisplatin-fibrin + CpG-ODN) increased the host/tumor cell ratio and CD8+ T-cell infiltration.
- Pro-inflammatory cytokine levels showed a trend towards increase with immuno-chemotherapy, but without statistical significance.
Conclusions:
- Adjuvant chemotherapy and immuno-chemotherapy effectively reduce mesothelioma recurrence post-surgery in a preclinical model.
- Immuno-chemotherapy promotes an anti-tumor immune response by increasing inflammatory cell recruitment.
- These findings support the potential of combining chemotherapy with immunotherapy for MPM management.
