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Updated: Dec 14, 2025
Orthotopic Implantation and Peripheral Immune Cell Monitoring in the II-45 Syngeneic Rat Mesothelioma Model
Published on: October 2, 2015
Preliminary study highlights the potential of immune checkpoint inhibitors in sarcomatoid mesothelioma
Natasha K Brockwell1,2,3, Muhammad Alamgeer4,5, Beena Kumar5
1Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia.
Background:
Malignant pleural mesothelioma (MPM) is well known as an aggressive disease with poor survival. This has sparked trials of alternate immune-based therapies in MPM. While up to a quarter of MPM patients respond to immune checkpoint inhibitors (ICIs), predicting response remains challenging and PD-L1 expression alone has been deemed insufficient. Additionally, patients with sarcomatoid MPM are often excluded from trials utilizing ICIs due to their rapid progression. Here, we analyze the association of T lymphocytes with response to ICI-based immunotherapy to uncover predictive immune markers across subtypes.
Methods:
Retrospective analysis of immunotherapy treated mesothelioma patient cohorts from two sites were pooled. Patient characteristics, including age, sex, subtype and previous treatment were captured. Multiplex immunohistochemistry was used to assess proportions of CD4, CD8, CD45RO and FOXP3 positive infiltrates in MPM and their association with progression free (PFS) and overall (OS) survival post immunotherapy.
Results:
Samples derived from 22 patients were analyzed; 13 (59%) had epithelioid MPM, 6 (27%) sarcomatoid and 3 (14%) biphasic. The overall ICI response rate was 40%, with a median PFS (mPFS) and OS (mOS) of 3.8 and 11.17 months, respectively. Of the subtypes, sarcomatoid patients displayed the greatest median PFS and OS (>28 months) post ICI compared to the epithelioid subtype (3 and 11 months respectively), which correlated with higher proportions of infiltrating CD8+, CD45RO+ and CD8+CD45RO+ cells. Patients who received ICIs as first-line therapy had greater PFS than those who received it as second or third line post-chemotherapy.
Conclusions:
High proportions of T lymphocytes and CD45RO+ cells were associated with prolonged mPFS and mOS in sarcomatoid patients treated with ICI immunotherapy. These data support the expansion of trials utilizing single and combination ICIs as first-line therapy in sarcomatoid MPM and warrants further studies testing the impact or detriment of chemotherapy pre-ICI.
Insights
Immune checkpoint inhibitors (ICIs) show promise for malignant pleural mesothelioma (MPM). High T lymphocyte and CD45RO+ cell counts predict better outcomes in sarcomatoid MPM, suggesting first-line ICI therapy for this subtype.
Area of Science:
- Oncology
- Immunotherapy
- Malignant Pleural Mesothelioma Research
Background:
- Malignant pleural mesothelioma (MPM) is an aggressive cancer with limited treatment options.
- Immune checkpoint inhibitors (ICIs) offer a response in some MPM patients, but predicting efficacy remains a challenge.
- Sarcomatoid MPM patients are often excluded from ICI trials due to rapid disease progression.
Purpose of the Study:
- To investigate the association between T lymphocyte infiltration and response to ICI immunotherapy in MPM.
- To identify predictive immune markers for ICI response across different MPM subtypes.
- To evaluate the impact of prior chemotherapy and line of therapy on ICI treatment outcomes.
Main Methods:
- Retrospective analysis of pooled MPM patient cohorts from two institutions.
- Multiplex immunohistochemistry to quantify CD4, CD8, CD45RO, and FOXP3 positive immune cells.
- Correlation of immune cell proportions with progression-free survival (PFS) and overall survival (OS) post-ICI therapy.
Main Results:
- Sarcomatoid MPM subtype showed significantly longer median PFS and OS (>28 months) compared to epithelioid MPM (3 and 11 months, respectively).
- Higher proportions of CD8+, CD45RO+, and CD8+CD45RO+ T cells correlated with improved PFS and OS in sarcomatoid MPM patients.
- First-line ICI therapy resulted in better PFS than second or third-line treatment post-chemotherapy.
Conclusions:
- Elevated T lymphocyte and CD45RO+ cell infiltration are associated with prolonged survival in sarcomatoid MPM patients receiving ICI immunotherapy.
- These findings support expanding clinical trials of ICIs as first-line therapy for sarcomatoid MPM.
- Further research is needed to understand the role of pre-ICI chemotherapy in MPM treatment outcomes.
