Extracellular vesicles in immunomodulation and tumor progression

Marar, Carolyn; Starich, Bartholomew; Wirtz, Denis

doi:10.1038/s41590-021-00899-0

Cited by 313 publications

(271 citation statements)

References 156 publications

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“…EVs can be stored for long durations, with reduced loss of function compared with cells applied in therapeutic strategies (25). Moreover, the cargo encapsulated by EVs or NVs has showed more stable functions than free cargo (26)(27)(28), suggesting the potential applications of EVs or NVs in drug delivery (29). Previous studies have shown that mechanical extrusion is a feasible method for producing NVs (30,31); in addition, NVs derived from M1 macrophages contain specific RNAs (5).…”

Section: Discussionmentioning

confidence: 99%

M1 Macrophage-Derived Nanovesicles Repolarize M2 Macrophages for Inhibiting the Development of Endometriosis

Yuan

Xue

et al. 2021

Front. Immunol.

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BackgroundEndometriosis is a common nonmalignant gynecological disorder that affects 10–15% women of reproductive age and causes several symptoms that result in decreased quality of life and a huge social burden. In recent decades, extracellular vesicles (EVs) have gained attention as a potential therapeutic tool; however, the therapeutic effects of EVs against endometriosis have not been reported. Accordingly, in this study, we investigated the feasibility of nanovesicles (NVs) derived from M1 macrophages (M1NVs) in treating endometriosis.MethodsM1NVs were prepared by serial extrusion. Co-culture assays were performed to investigate changes in tube formation and migration/invasion of eutopic endometrial stroma cells (ESCs) obtained from patients with endometriosis (EM-ESCs). A mouse model of endometriosis was established, and mice were treated with phosphate-buffered saline, M0NVs, or M1NVs to evaluate the efficacy and safety of M1NV for treating endometriosis.ResultsM1NVs directly or indirectly inhibited the migration and invasion of EM-ESCs and reduced tube formation. In the mouse model, M1NVs suppressed the development of endometriosis through reprogramming of M2 macrophages, without causing damage to the organs.ConclusionsM1NVs inhibit the development of endometriosis directly, or through repolarizing macrophages from M2 to M1 phenotype. Hence, administration of M1NVs may represent a novel method for the treatment of endometriosis.

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Section: Discussionmentioning

confidence: 99%

M1 Macrophage-Derived Nanovesicles Repolarize M2 Macrophages for Inhibiting the Development of Endometriosis

Yuan

Xue

et al. 2021

Front. Immunol.

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“…EVs have also been implicated in disease. Within the cancer field, EVs are associated with immune modulation and tumor progression (for review see Marar et al, 2021 ). EVs are also associated with various neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and prion diseases (Thompson et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles as a Means of Viral Immune Evasion, CNS Invasion, and Glia-Induced Neurodegeneration

Horn

MacLean

2021

Front. Cell. Neurosci.

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Extracellular vesicles (EVs) are small, membrane-bound vesicles released by cells as a means of intercellular communication. EVs transfer proteins, nucleic acids, and other biologically relevant molecules from one cell to another. In the context of viral infections, EVs can also contain viruses, viral proteins, and viral nucleic acids. While there is some evidence that the inclusion of viral components within EVs may be part of the host defense, much of the research in this field supports a pro-viral role for EVs. Packaging of viruses within EVs has repeatedly been shown to protect viruses from antibody neutralization while also allowing for their integration into cells otherwise impervious to the virus. EVs also bidirectionally cross the blood-brain barrier (BBB), providing a potential route for peripheral viruses to enter the brain while exiting EVs may serve as valuable biomarkers of neurological disease burden. Within the brain, EVs can alter glial activity, increase neuroinflammation, and induce neurotoxicity. The purpose of this mini-review is to summarize research related to viral manipulation of EV-mediated intercellular communication and how such manipulation may lead to infection of the central nervous system, chronic neuroinflammation, and neurodegeneration.

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“…Tumor-related immune responses play important roles in cell infiltration and metastasis in the tumor microenvironment (Marar et al, 2021;Zhu et al, 2021), whereas ferroptosis and lncRNAs play key regulatory roles in tumor-related immune responses Sun et al, 2020;Tang et al, 2020). The results of our immune-related GSEA analyses of the high-and low-risk groups revealed that the immune response and immune system processes were significantly enriched in the low-risk group, suggesting that low-risk patients have ferroptosisrelated, anti-tumor immune response processes that reduce the risk of death.…”

Section: Discussionmentioning

confidence: 99%

Identification and Validation of a Ferroptosis-Related Long Non-coding RNA Signature for Predicting the Outcome of Lung Adenocarcinoma

Zheng

Zhang

et al. 2021

Front. Genet.

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BackgroundFerroptosis is a recently recognized type of programmed cell death that is involved in the biological processes of various cancers. However, the mechanism of ferroptosis in lung adenocarcinoma (LUAD) remains unclear. This study aimed to determine the role of ferroptosis-associated long non-coding RNAs (lncRNAs) in LUAD and to establish a prognostic model.MethodsWe downloaded ferroptosis-related genes from the FerrDb database and RNA sequencing data and clinicopathological characteristics from The Cancer Genome Atlas. We randomly divided the data into training and validation sets. Ferroptosis-associated lncRNA signatures with the lowest Akaike information criteria were determined using COX regression analysis and the least absolute shrinkage and selection operator. The risk scores of ferroptosis-related lncRNAs were calculated, and patients with LUAD were assigned to high- and low-risk groups based on the median risk score. The prognostic value of the risk scores was evaluated using Kaplan–Meier curves, Cox regression analyses, and nomograms. We then explored relationships between ferroptosis-related lncRNAs and the immune response using gene set enrichment analysis (GSEA).ResultsTen ferroptosis-related lncRNA signatures were identified in the training group, and Kaplan–Meier and Cox regression analyses confirmed that the risk scores were independent predictors of LUAD outcome in the training and validation sets (all P < 0.05). The area under the curve confirmed that the signatures could determine the prognosis of LUAD. The predictive accuracy of the established nomogram model was verified using the concordance index and calibration curve. The GSEA showed that the 10 ferroptosis-related lncRNAs might be associated with tumor immune response.ConclusionWe established a novel signature involving 10 ferroptosis-related lncRNAs (LINC01843, MIR193BHG, AC091185.1, AC027031.2, AL021707.2, AL031667.3, AL606834.1, AC026355.1, AC124045.1, and AC025048.4) that can accurately predict the outcome of LUAD and are associated with the immune response. This will provide new insights into the development of new therapies for LUAD.

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Extracellular vesicles in immunomodulation and tumor progression

Cited by 313 publications

References 156 publications

M1 Macrophage-Derived Nanovesicles Repolarize M2 Macrophages for Inhibiting the Development of Endometriosis

M1 Macrophage-Derived Nanovesicles Repolarize M2 Macrophages for Inhibiting the Development of Endometriosis

Extracellular Vesicles as a Means of Viral Immune Evasion, CNS Invasion, and Glia-Induced Neurodegeneration

Identification and Validation of a Ferroptosis-Related Long Non-coding RNA Signature for Predicting the Outcome of Lung Adenocarcinoma

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