Malignant Pleural Mesothelioma: Current Understanding of the Immune Microenvironment and Treatments of a Rare Disease

Our plain-English summary of Malignant Pleural Mesothelioma: Current Understanding of the Immune Microenvironment and Treatments of a Rare Disease, by J. Tedesco, M. Jaradeh, W.T. Vigneswaran (Cancers, 2022).

The study

• Authors: J. Tedesco, M. Jaradeh, W.T. Vigneswaran
• Journal: Cancers
• Published: 2022;14(18)
• Type of article: Review
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma is a rare disease with an annual incidence of around 3000 cases a year in the United States. Most cases are caused by asbestos exposure, with a latency period of up to 40 years. Pleural mesothelioma is an aggressive disease process with overall survival of roughly 6-12 months after the time of diagnosis. It is divided into three subtypes: epithelioid, mixed type, and sarcomatoid type, with the epithelioid subtype having the best overall survival. Often, the treatment is multimodality with surgery, chemotherapy, and radiation. The survival benefit is improved but remains marginal. New treatment options involving targeted immune therapies appear to offer some promise. The tumor microenvironment is the ecosystem within the tumor that interacts and influences the host immune system. Understanding this complex interaction and how the host immune system is involved in the progression of the disease process is important to define and guide potential treatment options for this devastating and rare disease.

In plain English

This article was a review of published literature on malignant pleural mesothelioma. It covered epidemiology, how the disease develops, the immune environment inside tumors, and current and possible future treatments. It did not report new data of its own. Citing other sources, the review stated that more than 80% of mesothelioma cases are due to asbestos exposure, with a latency period of up to 40 years. It described occupational asbestos exposure as followed by an intense immune response. It summarized a study by Ujiie and colleagues on the epithelioid subtype. Among patients who had not received neoadjuvant chemotherapy, high numbers of CD163+ macrophages (a type of immune cell) in the tumor stroma were associated with poor survival. In the EMPHACIS trial of 456 patients, pemetrexed plus cisplatin gave longer overall survival than cisplatin alone (12.1 versus 9.3 months). In the DETERMINE trial, tremelimumab showed no improved overall survival in patients with relapsed disease. The authors concluded that immunotherapy is now becoming part of the treatment algorithm, but that specific targets are yet to be reliably identified.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Literature review (no original data)
• Who was studied: No study population of its own; the authors reviewed published studies and clinical trials on malignant pleural mesothelioma (MPM)
• Exposure: Asbestos exposure, mainly occupational, as the main cause of MPM according to the sources reviewed. No specific fiber types were named. The review cited studies reporting that an exposure dose threshold of 25 to 100 fibers per mL per year significantly increases MPM risk.
• Main results:
  • Citing other sources, the review stated that more than 80% of mesothelioma cases are due to asbestos exposure, with a latency period of up to 40 years.
  • The review described most MPM cases as due to occupational exposure to asbestos, followed by an intense immune response leading to malignant growth.
  • The sarcomatoid subtype makes up about a quarter of cases and is associated with poor prognosis. The epithelioid subtype, about 50% of cases, has the best prognosis.
  • In the Ujiie study cited by the review, CD163+ macrophages and their ratio with CD8 and CD20 lymphocytes were independent predictors of survival in epithelioid MPM. Among patients who had not undergone neoadjuvant chemotherapy, high stromal CD163+ macrophages (M2 tumor-associated macrophages) were associated with poor survival.
  • In the EMPHACIS trial (456 patients not eligible for curative surgery), overall survival was 12.1 months with pemetrexed plus cisplatin versus 9.3 months with cisplatin alone (p = 0.02).
  • In a multicenter randomized trial of patients with unresectable disease, adding bevacizumab to cisplatin/pemetrexed gave 18.8 versus 16.1 months overall survival compared with chemotherapy alone (p = 0.0167).
  • In the DETERMINE trial (569 patients with advanced unresectable pleural or peritoneal mesothelioma), the 382 patients given tremelimumab showed no improved overall survival in relapsed MPM.
  • In the CheckMate 743 trial (605 patients with previously untreated MPM), 2-year overall survival was 41% in the nivolumab plus ipilimumab arm versus 27% in the chemotherapy arm.
  • In a retrospective study by Erber et al. cited by the review, loss of BAP1 expression in mesothelial tumors had a sensitivity of 0.56 and a specificity of 1.00 for distinguishing malignant mesothelioma from benign tumors.
• The authors' conclusion: The authors concluded that immunotherapy is now becoming part of the treatment algorithm for pleural mesothelioma, but that specific targets are yet to be reliably identified. They added that better understanding of the host immune system's role is important for future treatment development.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Asbestos Exposure, Latency, Overall Survival, Epithelioid, Sarcomatoid, Chemotherapy, Tumor Microenvironment.

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• Surgical biology for the clinician: peritoneal mesothelioma: current understanding and management — T.C. Chua, T.D. Yan, et al. (2009)
• The Current Understanding Of Asbestos-Induced Epigenetic Changes Associated With Lung Cancer — Y.Y. Cheng, E.M. Rath, et al. (2020)
• The Challenge of Defining Treatment Standards for a Rare Disease: Malignant Peritoneal Mesothelioma — H.L. Kindler (2016)
• Priming the tumor immune microenvironment with chemo(radio)therapy: A systematic review across tumor types — T. van den Ende, H.G. van den Boorn, et al. (2020)
• The Immune Microenvironment in Mesothelioma: Mechanisms of Resistance to Immunotherapy — G.J. Chu, N. van Zandwijk, et al. (2019)

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