Pathological Characterization of Tumor Immune Microenvironment (TIME) in Malignant Pleural Mesothelioma

Our plain-English summary of Pathological Characterization of Tumor Immune Microenvironment (TIME) in Malignant Pleural Mesothelioma, by F. Napoli, A. Listì, V. Zambelli, et al (Cancers, 2021).

The study

• Authors: F. Napoli, A. Listì, V. Zambelli, G. Witel, P. Bironzo, M. Papotti, M. Volante, G. Scagliotti, L. Righi
• Journal: Cancers
• Published: 2021;13(11)
• Type of article: Review
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a rare and highly aggressive disease that arises from pleural mesothelial cells, characterized by a median survival of approximately 13-15 months after diagnosis. The primary cause of this disease is asbestos exposure and the main issues associated with it are late diagnosis and lack of effective therapies. Asbestos-induced cellular damage is associated with the generation of an inflammatory microenvironment that influences and supports tumor growth, possibly in association with patients' genetic predisposition and tumor genomic profile. The chronic inflammatory response to asbestos fibers leads to a unique tumor immune microenvironment (TIME) composed of a heterogeneous mixture of stromal, endothelial, and immune cells, and relative composition and interaction among them is suggested to bear prognostic and therapeutic implications. TIME in MPM is known to be constituted by immunosuppressive cells, such as type 2 tumor-associated macrophages and T regulatory lymphocytes, plus the expression of several immunosuppressive factors, such as tumor-associated PD-L1. Several studies in recent years have contributed to achieve a greater understanding of the pathogenetic mechanisms in tumor development and pathobiology of TIME, that opens the way to new therapeutic strategies. The study of TIME is fundamental in identifying appropriate prognostic and predictive tissue biomarkers. In the present review, we summarize the current knowledge about the pathological characterization of TIME in MPM.

In plain English

This article was a review, not a new study. The authors summarized published research on the tumor immune microenvironment (TIME) in malignant pleural mesothelioma. TIME is the mix of supporting tissue, blood-vessel cells and immune cells around the tumor. The authors described asbestos exposure as the primary cause of the disease. They summarized studies reporting that asbestos fibers swallowed by immune cells called macrophages remain undegraded, which keeps inflammation going. The review covered studies on connective tissue, fibroblasts, macrophages, T and B lymphocytes, suppressor cells, dendritic cells, checkpoint proteins such as PD-L1 and VISTA, and blood-vessel growth. One study it described, of 230 epithelioid mesothelioma patients, linked particular combinations of immune cells with worse or better overall survival. The review noted that in clinical trials PD-L1 testing showed limited value in predicting who benefits from immune checkpoint drugs. It also noted that earlier research had mostly used small, mixed series without conclusive results. The authors concluded that TIME has an emerging role in tumor growth and that specific biomarkers still need to be 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: narrative review of published literature
• Who was studied: No new patients were studied. The review covered published research on malignant pleural mesothelioma tumor tissue, pleural fluid, cell lines and clinical trials.
• Exposure: Asbestos exposure, described as the primary cause of malignant pleural mesothelioma. No specific fiber types are named. The review's main subject is the immune and stromal environment of the tumor, not exposure.
• Main results:
  • The review described earlier studies reporting that asbestos fibers taken up by macrophages remain undegraded, induce macrophage death, and are taken up again by nearby macrophages, keeping the inflammasome active.
  • The review reported a study by Ujiie and coworkers of 230 epithelioid mesothelioma patients. In that study, high CD163+ macrophages with low CD8+ T cells was an independent marker of worse overall survival. Low CD163+ macrophages with high CD20+ B cells was an independent marker of better overall survival.
  • The review reported a study by Muller et al. finding VISTA and PD-L1 expression, respectively, in 88% and 33% of epithelioid, 90% and 43% of biphasic, and 42% and 75% of sarcomatoid mesotheliomas. VISTA was linked to favorable survival and PD-L1 to unfavorable survival.
  • The review stated that in clinical trials of immune checkpoint inhibitors, PD-L1 expression showed limited value in predicting benefit. It stated that PD-L1 testing currently has no role as a clinical predictive biomarker in this disease.
  • The review reported a study by Chia and coworkers of tissue from 329 patients. In the epithelioid group, high CD31 density and high PDGF expression were associated with poor prognosis.
• The authors' conclusion: The authors concluded that TIME has an emerging role in disease development, immune regulation and growth in malignant pleural mesothelioma. They wrote that specific biomarkers still need to be identified before personalized immunotherapies can be developed.
• Limitations the authors state:
  • The authors stated that past research on the prognostic and predictive role of TIME used mainly small and heterogeneous series, with no conclusive data.
  • The authors noted that standard chromogen-based immunohistochemistry cannot use more than one or two markers per slide.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Mesothelial Cells, Median Survival, Asbestos Exposure, Macrophage, PD-L1, Biomarker.

Related studies

• Molecular and Histopathological Characterization of the Tumor Immune Microenvironment in Advanced Stage of Malignant Pleural Mesothelioma — N.S. Patil, L. Righi, et al. (2018)
• Characterization of the immune microenvironment in malignant pleural mesothelioma reveals prognostic subgroups of patients — N. Fusco, V. Vaira, et al. (2020)
• Malignant Peritoneal Mesothelioma: Characterization of the Inflammatory Response in the Tumor Microenvironment — S. Judge, P. Thomas, et al. (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)
• 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)

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