The Immune Microenvironment of Malignant Pleural Mesothelioma: A Literature Review

Our plain-English summary of The Immune Microenvironment of Malignant Pleural Mesothelioma: A Literature Review, by A.L. Désage, G. Karpathiou, M. Peoc'h, et al (Cancers, 2021).

The study

• Authors: A.L. Désage, G. Karpathiou, M. Peoc'h, M.E. Froudarakis
• Journal: Cancers
• Published: 2021;13(13)
• Type of article: Review
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare and aggressive tumour with a poor prognosis, associated with asbestos exposure. Nowadays, treatment is based on chemotherapy with a median overall survival of less than two years. This review highlights the main characteristics of the immune microenvironment in MPM with special emphasis on recent biological advances. The MPM microenvironment is highly infiltrated by tumour-associated macrophages, mainly M2-macrophages. In line with infiltration by M2-macrophages, which contribute to immune suppression, other effectors of innate immune response are deficient in MPM, such as dendritic cells or natural killer cells. On the other hand, tumour infiltrating lymphocytes (TILs) are also found in MPM, but CD4+ and CD8+ TILs might have decreased cytotoxic effects through T-regulators and high expression of immune checkpoints. Taken together, the immune microenvironment is particularly heterogeneous and can be considered as mainly immunotolerant or immunosuppressive. Therefore, identifying molecular vulnerabilities is particularly relevant to the improvement of patient outcomes and the assessment of promising treatment approaches.

In plain English

This article was a narrative literature review, not a new study. The authors summarized published research on the immune cells and immune 'checkpoint' molecules found in malignant pleural mesothelioma (MPM). They describe MPM as a tumour associated with asbestos exposure. The article did not say how studies were searched for or chosen. From the studies reviewed, the authors reported that MPM tumours contain many macrophages, mainly of the M2 type. Dendritic cells and natural killer cells appeared reduced or impaired. The anti-tumour activity of infiltrating T-cells was described as reduced by regulatory T-cells. The authors wrote that high levels of regulatory T-cells inside tumours were associated with shorter survival, and that the role of CD8+ T-cells remained unclear. They also wrote that checkpoint molecules were highly expressed. They described reviewed work suggesting macrophages are involved early in the immune response after asbestos exposure. The authors concluded that the MPM immune environment is complex and mainly immunotolerant or immunosuppressive. They said larger and further studies are needed.

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: Narrative literature review of published studies; no search or selection method is described
• Who was studied: Published laboratory, animal and patient studies on the immune microenvironment of malignant pleural mesothelioma; the review does not state how many studies were included or how they were selected
• Exposure: Not an exposure study. The review describes MPM as associated with asbestos exposure and summarizes other studies on how asbestos may affect immune cells. One of these was cited laboratory work with chrysotile on natural killer cells.
• Main results:
  • Reviewed studies found M2-macrophages to be highly present in pleural fluid and tissue samples from MPM patients
  • A reviewed study (Cornwall et al.) found that mesothelioma patients had lower amounts of circulating myeloid dendritic cells than healthy age- and gender-matched controls
  • The authors summarized that regulatory T-cells (Tregs) decrease the anti-tumour activity of CD4+ and CD8+ tumour-infiltrating lymphocytes
  • The authors wrote that high regulatory T-cell levels inside tumours are associated with shorter survival in MPM patients
  • The authors wrote that the role of CD8+ tumour-infiltrating lymphocytes remains unclear
  • The authors wrote that immune checkpoints are highly expressed in the MPM microenvironment
  • For blood-count ratios in MPM patients, the authors reported that evidence links a high neutrophil-to-lymphocyte ratio with poorer prognosis, but that findings conflict
  • The review cited the CheckMate 743 trial as a first-line treatment trial. In that trial, median overall survival was 18.1 months with nivolumab plus ipilimumab and 14.1 months with standard chemotherapy (HR = 0.74, p = 0.002).
• The authors' conclusion: The authors concluded that the immune microenvironment of MPM is complex and can be considered mainly immunotolerant or immunosuppressive. They added that it differs by histology and even within the same tumour.
• Limitations the authors state:
  • The authors stated that larger studies are needed before tumour-infiltrating lymphocytes can be used as prognostic markers
  • The authors stated that further studies are needed to establish precise prognostic values for blood-count ratios (NLR, PLR, LMR)

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Prognosis, Asbestos Exposure, Chemotherapy, Median Overall Survival, Macrophage.

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• Molecular and Histopathological Characterization of the Tumor Immune Microenvironment in Advanced Stage of Malignant Pleural Mesothelioma — N.S. Patil, L. Righi, et al. (2018)
• Tumor Immune Microenvironment and Genetic Alterations in Mesothelioma — S. Hiltbrunner, L. Mannarino, et al. (2021)
• Analysis of DNA methylation patterns in the tumor immune microenvironment of metastatic melanoma — S. Mitra, M. Lauss, et al. (2020)
• Characterization of the immune microenvironment in malignant pleural mesothelioma reveals prognostic subgroups of patients — N. Fusco, V. Vaira, et al. (2020)

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