Exosomal miRNAs in tumor microenvironment

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Abstract

Tumor microenvironment (TME) is the internal environment in which tumor cells survive, consisting of tumor cells, fibroblasts, endothelial cells, and immune cells, as well as non-cellular components, such as exosomes and cytokines. Exosomes are tiny extracellular vesicles (40-160nm) containing active substances, such as proteins, lipids and nucleic acids. Exosomes carry biologically active miRNAs to shuttle between tumor cells and TME, thereby affecting tumor development. Tumor-derived exosomal miRNAs induce matrix reprogramming in TME, creating a microenvironment that is conducive to tumor growth, metastasis, immune escape and chemotherapy resistance. In this review, we updated the role of exosomal miRNAs in the process of TME reshaping.

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Biogenesis and secretion of exosomes.

Joanna Kowal, Mercedes Tkach, Clotilde Théry (2014)

Although observed for several decades, the release of membrane-enclosed vesicles by cells into their surrounding environment has been the subject of increasing interest in the past few years, which led to the creation, in 2012, of a scientific society dedicated to the subject: the International Society for Extracellular Vesicles. Convincing evidence that vesicles allow exchange of complex information fuelled this rise in interest. But it has also become clear that different types of secreted vesicles co-exist, with different intracellular origins and modes of formation, and thus probably different compositions and functions. Exosomes are one sub-type of secreted vesicles. They form inside eukaryotic cells in multivesicular compartments, and are secreted when these compartments fuse with the plasma membrane. Interestingly, different families of molecules have been shown to allow intracellular formation of exosomes and their subsequent secretion, which suggests that even among exosomes different sub-types exist. Copyright © 2014 Elsevier Ltd. All rights reserved.

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Immune cells within the tumor microenvironment: biological functions and roles in cancer immunotherapy

Xu Lei, Yu Lei, Jin-Ke Li … (2019)

The immune cells within the tumor microenvironment (TME) play important roles in tumorigenesis. It has been known that these tumor associated immune cells may possess tumor-antagonizing or tumor-promoting functions. Although the tumor-antagonizing immune cells within TME tend to target and kill the cancer cells in the early stage of tumorigenesis, the cancer cells seems to eventually escape from immune surveillance and even inhibit the cytotoxic function of tumor-antagonizing immune cells through a variety of mechanisms. The immune evasion capability, as a new hallmark of cancer, accidently provides opportunities for new strategies of cancer therapy, namely harnessing the immune cells to battle the cancer cells. Recently, the administrations of immune checkpoint modulators (represented by anti-CTLA4 and anti-PD antibodies) and adoptive immune cells (represented by CAR-T) have exhibited unexpected antitumor effect in multiple types of cancer, bringing a new era for cancer therapy. Here, we review the biological functions of immune cells within TME and their roles in cancer immunotherapy, and discuss the perspectives of the basic studies for improving the effectiveness of the clinical use.

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Tumor Cell Biodiversity Drives Microenvironmental Reprogramming in Liver Cancer

Lichun Ma, Maria O. Hernandez, Yongmei Zhao … (2019)

Cellular diversity in tumors is key factor for therapeutic failures and lethal outcomes of solid malignancies. Here, we determined the single-cell transcriptomic landscape of liver cancer biospecimens from 19 patients. We found varying degrees of heterogeneity in malignant cells within and between tumors and diverse landscapes of tumor microenvironment (TME). Strikingly, tumors with higher transcriptomic diversity were associated with patient’s worse overall survival. We found a link between hypoxia-dependent VEGF expression in tumor diversity and TME polarization. Moreover, T cells from higher heterogenous tumors showed lower cytolytic activities. Consistent results were found using bulk genomic and transcriptomic profiles of 765 liver tumors. Our results offer insight into the diverse ecosystem of liver cancer and its impact on patient prognosis.

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Author and article information

Contributors

Yujuan Zhou: march-on@126.com

Qianjin Liao: yujany_zhou@163.com

Journal

Journal ID (nlm-ta): J Exp Clin Cancer Res

Journal ID (iso-abbrev): J. Exp. Clin. Cancer Res

Title: Journal of Experimental & Clinical Cancer Research : CR

Publisher: BioMed Central (London )

ISSN (Print): 0392-9078

ISSN (Electronic): 1756-9966

Publication date (Electronic): 16 April 2020

Publication date PMC-release: 16 April 2020

Publication date Collection: 2020

Volume: 39

Electronic Location Identifier: 67

Affiliations

[1 ]GRID grid.216417.7, ISNI 0000 0001 0379 7164, Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, , Central South University, ; 283 Tongzipo Road, Changsha, 410013 Hunan China

[2 ]GRID grid.412017.1, ISNI 0000 0001 0266 8918, University of South China, ; Hengyang, 421001 Hunan China

[3 ]GRID grid.280418.7, ISNI 0000 0001 0705 8684, Department of Medical Microbiology, , Immunology & Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, ; 913 N. Rutledge Street, Springfield, IL 62794, USA

Article

Publisher ID: 1570

DOI: 10.1186/s13046-020-01570-6

PMC ID: 7164281

PubMed ID: 32299469

SO-VID: 2cbf284a-a8ee-46bc-a400-96042d5ec0d6

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 10 January 2020

Date accepted : 6 April 2020

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;

Award ID: 81972636

Award ID: 81872281

Award Recipient : Yujuan Zhou Qianjin Liao

Funded by: FundRef http://dx.doi.org/10.13039/501100004735, Natural Science Foundation of Hunan Province;

Award ID: 2019JJ40175

Award ID: 2019JJ40183

Award ID: 2018JJ1013

Award Recipient : Jinguan Lin Yujuan Zhou Qianjin Liao

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: exosomal mirnas,tumor microenvironment (tme),cafs,angiogenesis,immune microenvironment

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ScienceOpen disciplines: Oncology & Radiotherapy

Keywords: exosomal mirnas, tumor microenvironment (tme), cafs, angiogenesis, immune microenvironment

Exosomal miRNAs in tumor microenvironment

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Abstract

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Karger: Oncology

Most cited references 102

Biogenesis and secretion of exosomes.

Immune cells within the tumor microenvironment: biological functions and roles in cancer immunotherapy

Tumor Cell Biodiversity Drives Microenvironmental Reprogramming in Liver Cancer

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