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dc.contributor.authorBrockwell, Natasha K-
dc.contributor.authorAlamgeer, Muhammad-
dc.contributor.authorKumar, Beena-
dc.contributor.authorRivalland, Gareth-
dc.contributor.authorJohn, Thomas-
dc.contributor.authorParker, Belinda S-
dc.identifier.citationTranslational Lung Cancer Research 2020; 9(3): 639-645en
dc.description.abstractMalignant 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.en
dc.subjectT cellsen
dc.subjectimmune infiltrateen
dc.titlePreliminary study highlights the potential of immune checkpoint inhibitors in sarcomatoid mesothelioma.en
dc.typeJournal Articleen
dc.identifier.journaltitleTranslational Lung Cancer Researchen
dc.identifier.affiliationOlivia Newton-John Cancer Research Instituteen
dc.identifier.affiliationSir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australiaen
dc.identifier.affiliationResearch Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australiaen
dc.identifier.affiliationDepartment of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria, Australiaen
dc.identifier.affiliationDepartment of Medical Oncology, Monash Medical Centre, Monash University, Clayton, Victoria, Australiaen
dc.identifier.affiliationMonash Health, Clayton, Victoria, Australiaen
dc.type.austinJournal Article
item.openairetypeJournal Article-
item.fulltextNo Fulltext-
item.cerifentitytypePublications- Newton-John Cancer Research Institute- Oncology- Newton-John Cancer Wellness and Research Centre-
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