Heterogeneity in Immune Cell Content in Malignant Pleural Mesothelioma

Our plain-English summary of Heterogeneity in Immune Cell Content in Malignant Pleural Mesothelioma, by J. Minnema-Luiting, H. Vroman, J. Aerts, et al (International Journal of Molecular Sciences, 2018).

The study

• Authors: J. Minnema-Luiting, H. Vroman, J. Aerts, R. Cornelissen
• Journal: International Journal of Molecular Sciences
• Published: 2018;19(4)
• Type of article: Review
• Cited by: 57 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant pleural mesothelioma (MPM) is a highly aggressive cancer with limited therapy options and dismal prognosis. In recent years, the role of immune cells within the tumor microenvironment (TME) has become a major area of interest. In this review, we discuss the current knowledge of heterogeneity in immune cell content and checkpoint expression in MPM in relation to prognosis and prediction of treatment efficacy. Generally, immune-suppressive cells such as M2 macrophages, myeloid-derived suppressor cells and regulatory T cells are present within the TME, with extensive heterogeneity in cell numbers. Infiltration of effector cells such as cytotoxic T cells, natural killer cells and T helper cells is commonly found, also with substantial patient to patient heterogeneity. PD-L1 expression also varied greatly (16-65%). The infiltration of immune cells in tumor and associated stroma holds key prognostic and predictive implications. As such, there is a strong rationale for thoroughly mapping the TME to better target therapy in mesothelioma. Researchers should be aware of the extensive possibilities that exist for a tumor to evade the cytotoxic killing from the immune system. Therefore, no "one size fits all" treatment is likely to be found and focus should lie on the heterogeneity of the tumors and TME.

In plain English

This article was a review, not a new study. The authors, from the Erasmus MC Cancer Institute in Rotterdam, searched the published literature on immune cells and immune 'checkpoint' proteins such as PD-L1 in malignant pleural mesothelioma. They looked at how these relate to survival and to treatment response. The review did not study asbestos exposure. In the studies they reviewed, macrophages (a type of immune cell) were found in all mesotheliomas examined, mostly of the M2 type, and M2 macrophages seemed to be linked with worse prognosis. Infiltration by cytotoxic T cells was associated with better prognosis in most studies. Numbers of T cells varied widely from patient to patient, and B cells were generally sparse. Across eight studies of PD-L1, the protein was found in 16% to 65% of mesotheliomas. It was found more often in non-epithelioid tumors (37.5 to 97.4%) than in epithelioid tumors (6.7 to 31%). The authors concluded that thoroughly mapping each tumor's immune makeup is a rational basis for targeting therapy, and that no 'one size fits all' treatment is likely to be found.

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 of published studies
• Who was studied: Published studies of malignant pleural mesothelioma tumor specimens and pleural effusions, including eight studies of PD-L1 expression; the review does not state search dates or the total number of studies
• Exposure: Not an exposure study; the review concerned immune cell content and immune checkpoint (PD-L1) expression in mesothelioma tumors, in relation to prognosis and treatment
• Main results:
  • Across the reviewed studies, macrophages were abundantly present in all mesotheliomas, with widely varying levels, and generally showed an M2 phenotype
  • In the reviewed studies, infiltration of M2 macrophages and PD-L1 expression seemed to be associated with worse prognosis
  • Infiltration of cytotoxic T cells was associated with better prognosis in most of the reviewed studies
  • In one reviewed study of 32 extrapleural pneumonectomy specimens taken after induction chemotherapy, the coefficient of variation of T cell counts ranged from 0.49 to 0.87, which the authors read as substantial heterogeneity
  • Across the eight PD-L1 studies, PD-L1 was expressed in 16% to 65% of malignant mesotheliomas, and more often in non-epithelioid than in epithelioid tumors (37.5 to 97.4% versus 6.7 to 31%)
  • B cell infiltration was generally sparse, although one subgroup with higher numbers of B cells was described
  • Significant numbers of regulatory T cells (Tregs) were found in mesothelioma biopsies and pleural fluid
• The authors' conclusion: The authors concluded that thoroughly mapping the tumor microenvironment is rational for targeting therapy, and that no 'one size fits all' treatment is likely to be found, so focus should be on the heterogeneity of tumors and their microenvironment
• Limitations the authors state:
  • The authors stated that more research is needed to determine the clinical implications of B cell infiltration

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Prognosis, Tumor Microenvironment, Macrophage, PD-L1, Mesothelioma.

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• Heterogeneity in immunologic functions of rat alveolar macrophages--their accessory cell function and IL-1 production — Y. Oghiso (1987)
• Unraveling tumor microenvironment heterogeneity in malignant pleural mesothelioma identifies biologically distinct immune subtypes enabling prognosis determination — K. Yang, T. Yang, et al. (2022)
• V-domain Ig-containing suppressor of T-cell activation (VISTA), a potentially targetable immune checkpoint molecule, is highly expressed in epithelioid malignant pleural mesothelioma — S. Muller, W. Victoria Lai, et al. (2020)

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