Mesothelial cells regulate immune responses in health and disease: role for immunotherapy in malignant mesothelioma

Our plain-English summary of Mesothelial cells regulate immune responses in health and disease: role for immunotherapy in malignant mesothelioma, by S.E. Mutsaers, F.J. Pixley, C.M. Prêle, et al (Current Opinion in Immunology, 2020).

The study

• Authors: S.E. Mutsaers, F.J. Pixley, C.M. Prêle, G.F. Hoyne
• Journal: Current Opinion in Immunology
• Published: 2020;64:88-109
• Type of article: Review
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The mesothelium when first described was thought to function purely as a non-adhesive surface to facilitate intracoelomic movement of organs. However, the mesothelium is now recognized as a dynamic cellular membrane with many important functions that maintain serosal integrity and homeostasis. For example, mesothelial cells interact with and help regulate the body's inflammatory and immune system following infection, injury, or malignancy. With recent advances in our understanding of checkpoint molecules and the advent of novel immunotherapy approaches, there has been an increase in the number of studies examining mesothelial and immune cell interaction, in particular the role of these interactions in malignant mesothelioma. This review will highlight some of the recent advances in our understanding of how mesothelial cells help regulate serosal immunity and how in a malignant environment, the immune system is hijacked to stimulate tumor growth. Ways to treat mesothelioma using immunotherapy approaches will also be discussed.

Copyright © 2020 Elsevier Ltd. All rights reserved.

In plain English

This article is a review, not a new study. The authors summarised recent research on how mesothelial cells interact with the immune system, and how in malignant mesothelioma (MM) the immune system is turned to promote tumor growth. They also discussed immunotherapy treatments. The review states that MM is strongly associated with asbestos exposure and fiber-associated inflammation, but it did not itself study asbestos exposure. It described results reported by other researchers. In the MERIT trial of nivolumab in malignant pleural mesothelioma, 29% of patients had an objective response. The PROMISE-meso trial of pembrolizumab did not show improved median overall survival or progression-free survival compared with chemotherapy. The objective response rate with avelumab in the JAVELIN trial was 9%. Tremelimumab showed no benefit over placebo in the DETERMINE trial. A table listed clinical trials registered on ClinicalTrials.gov. The authors suggested that checkpoint immunotherapy is likely to need combining with other treatments. They concluded that a better understanding of immune regulation is needed, pointing to the repeated lack of success of trials run without a sound scientific rationale.

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: Review article (narrative review of published research and registered clinical trials)
• Who was studied: No study population of its own. The authors reviewed published studies on mesothelial cells, immune cells and malignant mesothelioma, and in Table 1 listed mesothelioma clinical trials registered on ClinicalTrials.gov when the manuscript was prepared.
• Exposure: Not an exposure study. The review notes that MM is strongly associated with asbestos exposure and fiber-associated inflammation; no fiber types are named. Its focus is on immunotherapies, including checkpoint inhibitors, CAR-T cells and mesothelin-targeted therapies.
• Main results:
  • The review reports that in the MERIT study, a phase II trial of nivolumab in malignant pleural mesothelioma (not this review's own data), 29% of patients had an objective response.
  • The review reports that the phase III PROMISE-meso trial comparing pembrolizumab with single-agent chemotherapy failed to show improved median overall survival and progression-free survival.
  • The review reports that the objective response rate with avelumab in the phase 1 JAVELIN solid tumor trial in mesothelioma patients was 9%.
  • The review reports that tremelimumab, an anti-CTLA-4 therapy, showed no benefit over placebo in the DETERMINE trial.
  • The review reports that, overall, about 30% of patients receiving checkpoint inhibitor immunotherapy show a beneficial response.
  • The review reports that mesothelin-targeted CAR-T cells used in a phase 1 MM study were well tolerated but had limited clinical activity.
  • The review reports that the anti-mesothelin drug conjugate anetumab ravtansine failed to improve progression-free survival compared with vinorelbine in advanced malignant pleural mesothelioma.
  • The authors suggested that, to improve outcomes, checkpoint immunotherapy is likely to need combining with surgery, chemotherapy, signaling inhibitors and other immune approaches.
• The authors' conclusion: The authors concluded that understanding how the immune system is regulated in normal and diseased serosal tissue will be crucial for developing new therapies for MM. They considered this particularly important given the repeated lack of success of clinical trials of treatment combinations run without a sound scientific rationale.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Immunotherapy, Malignant Mesothelioma, Mesothelium, Mesothelioma.

Related studies

• Simian virus 40 infection down-regulates the expression of nitric oxide synthase in human mesothelial cells — E. Aldieri, S. Orecchia, et al. (2004)
• T cell receptor repertoire characteristics both before and following immunotherapy correlate with clinical response in mesothelioma — H. Vroman, G. Balzaretti, et al. (2020)
• WT1 peptide vaccinations induce CD4 and CD8 T cell immune responses in patients with mesothelioma and non-small cell lung cancer — L.M. Krug, T. Dao, et al. (2010)
• Chemical agents and the immune response — M.I. Luster, G.J. Rosenthal (1993)
• Microbiomes, Epigenomics, Immune Response, and Splicing Signatures Interplay: Potential Use of Combination of Regulatory Pathways as Targets for Malignant Mesothelioma — B.P. Setlai, Z.L. Mkhize-Kwitshana, et al. (2022)
• Increased epidermal growth factor-receptor protein in a human mesothelial cell line in response to long asbestos fibers — J.C. Pache, Y.M. Janssen, et al. (1998)

Browse return to medical research.