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Extracellular Vesicles and Their Role in Immunomodulation and Cancer

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 8585

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Special Issue Editor

Dr. Milad Moloudizargari

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Guest Editor

Beckman Research Institute of City of Hope, Monrovia, CA 91010, USA
Interests: cancer immunology; extracellular vesicles; tumor-derived exosomes; immunomodulation; immunotherapy; multiple myeloma; tumor microenvironment; natural killer cells

Special Issue Information

Dear Colleagues,

Today, a great deal of evidence has shown the critical role of extracellular vesicles (EVs) in tumor progression and host immune response. Among different subtypes of EVs, categorized mainly based on their size, small EVs, also known as exosomes, have been at the center of attention in recent years due to their ever-expanding role in tumor metastasis and drug resistance, as well as the modulation of antitumor immune responses. In this context, exosomes have been shown to be capable of both stimulating and dampening antitumor immune responses, making them a double-edged sword in cancer management. Furthermore, the absence of a consensus on specific markers for the identification of exosomes adds to the complexity of their study and opens up a potential area for future cancer research. In addition to their potential for therapeutic targeting in cancer, there is growing evidence for the potential of exosomes as rich sources of diagnostic markers, which provide superior advantages as sources of cancer biomarkers for liquid-biopsy-based assays. Accordingly, a Special Issue entitled “Extracellular Vesicles and Their Role in Immunomodulation and Cancer” is launched to call forth scientists from all over the world to contribute their latest high-quality research for a better understanding of the field. Indeed, the successful completion of this Special Issue will spread the latest advances in the field to a wide readership.

In this Special Issue, rigorously prepared original research papers and critical reviews presenting novel findings on the most recent aspects of the field are welcome. The topics covered in this Special Issue include, but are not limited to:

EVs as modulators of the tumor microenvironment and the immune response.
Differences among EV sources and their biological relevance.
Engineering EV-producing cells as a tool for EV modification.
The prognostic and diagnostic potential of EVs as sources of immune markers in cancer.

Dr. Milad Moloudizargari
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

extracellular vesicles
cancer immunology
exosomes
tumor-derived exosomes
tumor escape
immunomodulation
immunotherapy
multiple myeloma
tumor microenvironment
diagnosis
biomarker
natural killer cells

Published Papers (4 papers)

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Research

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12 pages, 2303 KiB

Open AccessArticle

Isolation and Characterization of Extracellular Vesicles in Human Bowel Lavage Fluid

by Marina Alorda-Clara, Jose Reyes, Marita Grimanesa Trelles-Guzman, Monica Florido, Pilar Roca, Daniel Gabriel Pons and Jordi Oliver

Int. J. Mol. Sci. 2023, 24(8), 7391; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24087391 - 17 Apr 2023

Cited by 2 | Viewed by 1356

Abstract

Colorectal cancer (CRC) is the third most common cancer worldwide and is detected in late stages because of a lack of early and specific biomarkers. Tumors can release extracellular vesicles (EVs), which participate in different functions, such as carrying nucleic acids to target cells; promoting angiogenesis, invasion, and metastasis; and preparing an adequate tumor microenvironment. Finally, bowel lavage fluid (BLF) is a rarely used sample that is obtained during colonoscopy. It presents low variability and protein degradation, is easy to handle, and is representative of EVs from tumor cells due to proximity of the sample collection. This sample has potential as a research tool and possible biomarker source for CRC prognosis and monitoring. In this study, EVs were isolated from human BLF by ultracentrifugation, then characterized by transmission electron microscopy and atomic force microscopy. EV concentration was determined by nanoparticle tracking analysis, and tetraspanins were determined by Western blot, confirming correct EV isolation. RNA, DNA, and proteins were isolated from these EVs; RNA was used in real-time PCR, and proteins were used in an immunoblotting analysis, indicating that EV cargo is optimal for use and study. These results indicate that EVs from BLF can be a useful tool for CRC study and could be a source of biomarkers for the diagnosis and monitoring of CRC. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Their Role in Immunomodulation and Cancer)

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16 pages, 3878 KiB

Open AccessArticle

miR-221-5p and miR-186-5p Are the Critical Bladder Cancer Derived Exosomal miRNAs in Natural Killer Cell Dysfunction

by Ting Huyan, Lina Gao, Na Gao, Chaochao Wang, Wuli Guo, Xiaojie Zhou and Qi Li

Int. J. Mol. Sci. 2022, 23(23), 15177; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232315177 - 02 Dec 2022

Cited by 7 | Viewed by 1837

Abstract

Bladder cancer (BC) is the tenth most commonly diagnosed cancer worldwide, and its carcinogenesis mechanism has not been fully elucidated. BC is able to induce natural killer (NK) cell dysfunction and escape immune surveillance. The present study found that exosomes derived from the urinary bladder cancer cell line (T24 cell) contribute in generating NK cell dysfunction by impairing viability, and inhibiting the cytotoxicity of the NK cell on target cells. Meanwhile, T24 cell-derived exosomes inhibited the expression of the important functional receptors NKG2D, NKp30, and CD226 on NK cells as well as the secretion of perforin and granzyme-B. The critical miRNAs with high expression in T24 cell-derived exosomes were identified using high-throughput sequencing. Furthermore, following dual-luciferase reporter assay and transfection experiments, miR-221-5p and miR-186-5p were confirmed as interfering with the stability of the mRNAs of DAP10, CD96, and the perforin gene in NK cells and may be potential targets used in the therapy for BC. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Their Role in Immunomodulation and Cancer)

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21 pages, 3243 KiB

Open AccessArticle

Differential Immunomodulatory Effects of Head and Neck Cancer-Derived Exosomes on B Cells in the Presence of ATP

by Mali Coray, Veronika Göldi, Lukas Schmid, Laura Benecke, Fabrício Figueiró and Laurent Muller

Int. J. Mol. Sci. 2022, 23(22), 14446; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232214446 - 21 Nov 2022

Cited by 1 | Viewed by 1356

Abstract

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy. Tumor-derived exosomes (TEX) have immunoregulatory properties. Adenosine triphosphate (ATP) and its immunosuppressive precursor adenosine (ADO) have been found in cancerous tissue. We investigated the effect of TEX on B cells in the presence of ATP. TEX were isolated from human HNSCC cell line (PCI-13) cultures and co-cultured with peripheral blood B cells of healthy donors, with or without TEX in different concentrations and with or without a low (20 µM) or high (2000 µM) ATP dose. We were able to demonstrate that TEX inhibit B-cell proliferation. The addition of TEX to either ATP concentration showed a decreasing trend in CD39 expression on B cells in a dose-dependent manner. High ATP levels (2000 µM) increased apoptosis and necrosis, and analysis of apoptosis-associated proteins revealed dose-dependent effects of ATP, which were modified by TEX. Altogether, TEX exhibited dual immunomodulatory effects on B cells. TEX were immunosuppressive by inhibiting B-cell proliferation; they were immunostimulatory by downregulating CD39 expression. Furthermore, TEX were able to modulate the expression of pro- and anti-apoptotic proteins. In conclusion, our data indicate that TEX play an important, but complex, role in the tumor microenvironment. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Their Role in Immunomodulation and Cancer)

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Review

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31 pages, 2805 KiB

Open AccessReview

Hypoxia-Regulated Tumor-Derived Exosomes and Tumor Progression: A Focus on Immune Evasion

by Xuejun Shao, Shenghao Hua, Tao Feng, Dickson Kofi Wiredu Ocansey and Lei Yin

Int. J. Mol. Sci. 2022, 23(19), 11789; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231911789 - 04 Oct 2022

Cited by 12 | Viewed by 3488

Abstract

Tumor cells express a high quantity of exosomes packaged with unique cargos under hypoxia, an important characteristic feature in solid tumors. These hypoxic tumor-derived exosomes are, crucially, involved in the interaction of cancer cells with their microenvironment, facilitating not only immune evasion, but increased cell growth and survival, enhanced angiogenesis, epithelial–mesenchymal transition (EMT), therapeutic resistance, autophagy, pre-metastasis, and metastasis. This paper explores the tumor microenvironment (TME) remodeling effects of hypoxic tumor-derived exosome towards facilitating the tumor progression process, particularly, the modulatory role of these factors on tumor cell immune evasion through suppression of immune cells, expression of surface recognition molecules, and secretion of antitumor soluble factor. Tumor-expressed exosomes educate immune effector cells, including macrophages, monocytes, T cells, natural killer (NK) cells, dendritic cells (DCs), γδ T lymphocytes, regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), mast cells, and B cells, within the hypoxic TME through the release of factors that regulate their recruitment, phenotype, and function. Thus, both hypoxia and tumor-derived exosomes modulate immune cells, growth factors, cytokines, receptor molecules, and other soluble factors, which, together, collaborate to form the immune-suppressive milieu of the tumor environment. Exploring the contribution of exosomal cargos, such as RNAs and proteins, as indispensable players in the cross-talk within the hypoxic tumor microenvironmental provides a potential target for antitumor immunity or subverting immune evasion and enhancing tumor therapies. Full article

(This article belongs to the Special Issue Extracellular Vesicles and Their Role in Immunomodulation and Cancer)

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