Mesothelioma Malignancy and the Microenvironment: Molecular Mechanisms

Our plain-English summary of Mesothelioma Malignancy and the Microenvironment: Molecular Mechanisms, by F. Cersosimo, M. Barbarino, S. Lonardi, et al (Cancers, 2021).

The study

• Authors: F. Cersosimo, M. Barbarino, S. Lonardi, W. Vermi, A. Giordano, C. Bellan, E. Giurisato
• Journal: Cancers
• Published: 2021;13(22)
• Type of article: Review
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Several studies have reported that cellular and soluble components of the tumor microenvironment (TME) play a key role in cancer-initiation and progression. Considering the relevance and the complexity of TME in cancer biology, recent research has focused on the investigation of the TME content, in terms of players and informational exchange. Understanding the crosstalk between tumor and non-tumor cells is crucial to design more beneficial anti-cancer therapeutic strategies. Malignant pleural mesothelioma (MPM) is a complex and heterogenous tumor mainly caused by asbestos exposure with few treatment options and low life expectancy after standard therapy. MPM leukocyte infiltration is rich in macrophages. Given the failure of macrophages to eliminate asbestos fibers, these immune cells accumulate in pleural cavity leading to the establishment of a unique inflammatory environment and to the malignant transformation of mesothelial cells. In this inflammatory landscape, stromal and immune cells play a driven role to support tumor development and progression via a bidirectional communication with tumor cells. Characterization of the MPM microenvironment (MPM-ME) may be useful to understand the complexity of mesothelioma biology, such as to identify new molecular druggable targets, with the aim to improve the outcome of the disease. In this review, we summarize the known evidence about the MPM-ME network, including its prognostic and therapeutic relevance.

In plain English

This article was a review, not a new study of patients or workers. The authors summarized published research on the microenvironment of malignant pleural mesothelioma: the immune cells, connective-tissue (stromal) cells and signaling molecules surrounding the tumor. They described the disease as mainly related to asbestos fiber exposure. They also noted that cases had been reported in chronic inflammatory conditions without fiber exposure. The review described the failure of macrophages (scavenger immune cells) to clear asbestos fibers as one possible mechanism promoting cancerous change in mesothelial cells. According to the studies reviewed, tumor-associated macrophages were the most abundant immune cells in mesothelioma, and their high prevalence had been associated with poor prognosis. High density of CD8+ T cells had been linked to improved outcomes. The review also covered cancer stem cells and drug resistance, differences between tumor subtypes, and treatments tested in clinical trials. The authors concluded that therapies targeting the microenvironment were promising but that their efficacy remained limited. They also said that some areas, such as how macrophages are regulated in mesothelioma, had little evidence.

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 review of published research. The article does not describe a literature search method.
• Who was studied: No study population. The review covered published laboratory, animal and clinical research on the tumor microenvironment of malignant pleural mesothelioma (MPM).
• Exposure: Asbestos fibers in general, described as the main external cause of MPM. No specific fiber types, products, jobs or doses are studied.
• Main results:
  • From the literature reviewed: failed phagocytosis (failed engulfing) of asbestos fibers by macrophages was described as one possible mechanism promoting cancerous transformation of mesothelial cells.
  • From the literature reviewed: mesothelioma cases had also been reported in chronic inflammatory conditions without fiber exposure.
  • From the literature reviewed: tumor-associated macrophages were the most abundant immune cells in mesothelioma, and their high prevalence was associated with poor prognosis in mesothelioma patients.
  • From the literature reviewed: high density of CD8+ immune cells was linked to improved outcomes in MPM patients.
  • From the literature reviewed: deletion of the CDKN2A gene was described as the most common mutation in mesothelioma, in approximately 70% of MPM cases.
  • From the literature reviewed: in phase II-III trials, bevacizumab added to pemetrexed plus cisplatin showed a significant improvement in overall survival in patients with advanced MPM.
  • From the literature reviewed: the CTLA-4 inhibitors tremelimumab and ipilimumab, tested in clinical trials, showed no improvement in overall survival for mesothelioma patients.
• The authors' conclusion: The authors concluded that therapies targeting the tumor microenvironment, including immunotherapy and combined immuno-chemotherapy, were promising approaches but that their efficacy remained limited.
• Limitations the authors state:
  • The authors stated that there was little evidence on the molecular mechanisms regulating tumor-associated macrophages in mesothelioma, and that few therapies targeting them had been developed.
  • The authors stated that adenosine signaling had been poorly investigated in MPM.
  • The authors stated that the relationship between microenvironment variability and response to therapy in MPM required more investigation.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Tumor Microenvironment, Pleural Mesothelioma, Asbestos Exposure, Life Expectancy, Macrophage, Pleural Cavity, Malignant Transformation.

Related studies

• The Immune Microenvironment in Mesothelioma: Mechanisms of Resistance to Immunotherapy — G.J. Chu, N. van Zandwijk, et al. (2019)
• Molecular and Histopathological Characterization of the Tumor Immune Microenvironment in Advanced Stage of Malignant Pleural Mesothelioma — N.S. Patil, L. Righi, et al. (2018)
• Mechanism of miR-222 and miR-126 regulation and its role in asbestos-induced malignancy — S. Gaetani, F. Monaco, et al. (2020)
• Molecular pathways: targeting mechanisms of asbestos and erionite carcinogenesis in mesothelioma — M. Carbone, H. Yang (2012)
• Cellular and molecular mechanisms of asbestos-induced fibrosis — R. Robledo, B. Mossman (1999)
• Possible cellular and molecular mechanisms for asbestos carcinogenicity — C. Walker, J. Everitt, et al. (1992)

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