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Title: Preliminary study highlights the potential of immune checkpoint inhibitors in sarcomatoid mesothelioma.
Austin Authors: Brockwell, Natasha K;Alamgeer, Muhammad;Kumar, Beena;Rivalland, Gareth;John, Thomas ;Parker, Belinda S
Affiliation: Olivia Newton-John Cancer Research Institute
Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia
Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australia
Department of Medical Oncology, Monash Medical Centre, Monash University, Clayton, Victoria, Australia
Monash Health, Clayton, Victoria, Australia
Issue Date: Jun-2020
Date: 2020-06
Publication information: Translational Lung Cancer Research 2020; 9(3): 639-645
Abstract: 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. 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. 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. 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.
DOI: 10.21037/tlcr-19-485
Journal: Translational Lung Cancer Research
PubMed URL: 32676326
ISSN: 2218-6751
Type: Journal Article
Subjects: Immunotherapy
T cells
immune infiltrate
Appears in Collections:Journal articles

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