Critical Roles of Tumor Extracellular Vesicles in the Microenvironment of Thoracic Cancers

Our plain-English summary of Critical Roles of Tumor Extracellular Vesicles in the Microenvironment of Thoracic Cancers, by L. Kara-Terki, L. Treps, C. Blanquart, et al (International Journal of Molecular Sciences, 2020).

The study

• Authors: L. Kara-Terki, L. Treps, C. Blanquart, D. Fradin
• Journal: International Journal of Molecular Sciences
• Published: 2020;21(17)
• Type of article: Review
• Cited by: 16 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Extracellular vesicles (EVs), such as exosomes, are critical mediators of intercellular communication between tumor cells and other cells located in the microenvironment but also in more distant sites. Exosomes are small EVs that can carry a variety of molecules, such as lipids, proteins, and non-coding RNA, especially microRNAs (miRNAs). In thoracic cancers, including lung cancers and malignant pleural mesothelioma, EVs contribute to the immune-suppressive tumor microenvironment and to tumor growth and metastasis. In this review, we discuss the recent understanding of how exosomes behave in thoracic cancers and how and why they are promising liquid biomarkers for diagnosis, prognosis, and therapy, with a special focus on exosomal miRNAs.

In plain English

This article was a review, not a new study. The authors summarized published research on extracellular vesicles, including exosomes (tiny particles released by cells that carry proteins and genetic material such as microRNAs), in lung cancers and malignant pleural mesothelioma (MPM). The article did not study asbestos exposure itself; its introduction noted that asbestos fibers have long been associated with MPM. Among the reviewed studies, one reported that MPM-derived exosomes reduced the immune receptor NKG2D on natural killer and CD8+ T cells. Cavalleri et al. reported that two exosomal microRNAs, miR-103a-3p and miR-30e-3p, distinguished MPM patients from non-cancerous people exposed to asbestos fibers. The authors noted that the literature on MPM-derived exosomes in blood-vessel growth was sparser than for lung cancer, that lung cancer studies each found different microRNA panels, making interpretation difficult, and that some studies did not characterize exosomes by current guidelines. A reviewed phase II trial in 22 patients with non-small cell lung cancer showed no objective tumor response. The authors concluded that identifying exosomal microRNAs involved in tumor communication is necessary to develop new therapies.

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 laboratory, animal and clinical studies on tumor extracellular vesicles (exosomes) in thoracic cancers
• Who was studied: No study population of its own. The review covered published studies on lung cancers (small-cell and non-small cell) and malignant pleural mesothelioma (MPM): cell lines, animal models and patient samples such as plasma, serum, pleural effusions and bronchoalveolar lavage
• Exposure: Not an exposure study. The subject was extracellular vesicles released by tumor cells and their cargo (proteins, microRNAs). Asbestos appears in the introduction as long associated with MPM, and in one reviewed biomarker study that included asbestos-exposed people without cancer. No fiber types or doses are given.
• Main results:
  • Reviewed study (Cavalleri et al.): exosomal miR-103a-3p and miR-30e-3p discriminated MPM patients from non-cancerous individuals exposed to asbestos fibers
  • Reviewed study (Clayton et al.): MPM-derived exosomes reduced expression of NKG2D by NK cells and CD8+ T cells through transfer of TGF-β1
  • Reviewed study (Clayton et al.): exosomes from the pleural fluid of MPM patients expressed CD39 and CD73, receptors that can produce adenosine and downregulate T cell function
  • Reviewed study (Greening et al.): exosomes from MPM increased invasion by human umbilical vein endothelial cells and blood-vessel formation in laboratory assays, compared with control-treated cells
  • Reviewed study (Munson et al.): the most abundant microRNAs in MPM-derived exosomes were tumor suppressors, in particular miR-16-5p
  • Reviewed study (Huang et al.): 80% of non-small cell lung cancer exosomes were positive for EGFR, compared with 2% of exosomes from chronic lung inflammation
  • Reviewed study (Sandfeld-Paulsen et al.): in plasma samples from 276 non-small cell lung cancer patients, NY-ESO-1 was the only exosomal protein marker that kept a significant link with poorer survival after correction for multiple testing
  • Reviewed phase II trial of interferon-loaded dendritic cell-derived exosomes in 22 non-small cell lung cancer patients: generally well tolerated (one patient had grade 3 liver toxicity), with limited clinical outcomes and no objective tumor response
• The authors' conclusion: The authors concluded that extracellular vesicles play a role in cell interactions within the tumor microenvironment that lead to tumor growth and immune evasion, and that identifying the exosomal microRNAs involved is necessary to develop new directed therapies
• Limitations the authors state:
  • Studies of microRNA biomarker panels each identified their own panels, which made interpretation difficult
  • Some reviewed studies did not characterize exosomes according to the MISEV guidelines, so their samples are probably a mix of extracellular vesicles
  • In the section on blood-vessel formation (angiogenesis), the authors noted that the literature on MPM-derived exosomes is sparser than for lung cancer
  • Knowledge of how RNA is sorted into vesicles is too limited for clinical application

Topics

Medical terms in this study, explained in our Lexicon: Lung Cancer, Pleural Mesothelioma, Tumor Microenvironment, Metastasis, Biomarker, Prognosis.

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• Diagnostic and Prognostic Utility of the Extracellular Vesicles Subpopulations Present in Pleural Effusion — J. Javadi, A. Görgens, et al. (2021)
• Extracellular Vesicles Isolated from Malignant Mesothelioma Cancer-Associated Fibroblasts Induce Pro-Oncogenic Changes in Healthy Mesothelial Cells — T. Chernova, S. Grosso, et al. (2022)
• EZH2 Inhibition in Mesothelioma Cells Increases the Release of Extracellular Vesicles That Skew Neutrophils Toward a Protumor Phenotype — G. Pinton, E. Bari, et al. (2025)
• Exploring RNA cargo in extracellular vesicles for pleural mesothelioma detection — A. Kraft, M.B. Kirschner, et al. (2025)

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