Research progress of exosomes in tumor immune microenvironment

In recent decades, extracellular vesicles (EVs), as the main medium of intercellular communication, have participated in a variety of important physiological and pathological processes, and have attracted great attention
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They are secreted by almost all types of cells and carry biologically active substances, such as proteins, lipids, and nucleic acids, which can be passed from host cells to recipient cells, thereby triggering changes in the phenotype and function of the recipient cells
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Recent studies have shown that EVS plays an important role in reshaping the tumor immune microenvironment (TIME)
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EVs derived from tumor cells and immune cells mediate the communication between the proximal and distal ends, determining the fate of the tumor and the efficacy of anti-tumor
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This article reviews the role of EVS in remodeling time and regulating tumor-specific immunity and its research status
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The author mainly discusses the mutual regulation of EVS delivery between tumor cells and tumor infiltrating immune cells, and also describes the limitations of current research and discusses the direction of further research
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Image source: https://doi.
org/10.
1016/j.
canlet.
2021.
05.
032

Tumors include not only different subgroups of tumor cells, but also tumor-related fibroblasts, natural and acquired immune cells (such as monocytes/macrophages, dendritic cells, neutrophils, myeloid suppressor cells, Natural killer cells, T cells and B cells), vascular system, secreted factors and extensive extracellular matrix (ECM) network are collectively referred to as the tumor microenvironment (TME)
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Acidity, hypoxia and nutritional deficiencies are common features of TME, which provide strong selective pressure during tumor progression
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Tumors develop in a harsh and complex tumor microenvironment, and cell-to-cell communication occurs through various signal networks, which play a key role in tumor progression and metastasis
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Intercellular communication mediators in TME include cytokines, chemokines, growth factors, signal molecules and their receptors, tumor cells and mesenchymal cells, and extracellular vesicles
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Extracellular vesicles (EVs) are membrane-encapsulated vesicles that can be secreted by almost all types of cells.
They can transfer biologically active substances (such as proteins, nucleic acids, lipids, and metabolites) from the host cell to adjacent recipient cells And remote recipient cells, thereby coordinating a permanent communication network in the extracellular space
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Enteroviruses are widely present in body fluids such as blood, urine, saliva and breast milk.
They have the characteristics of biocompatibility, biological barrier permeability, low toxicity and low immunogenicity
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Because of these unique characteristics, the EV is considered promising clinical biomarkers and nano- carriers , the disease can be non-invasive early diagnosis , monitoring and treatment
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Ev was originally considered as a "waste disposal method" to remove unwanted cellular components; instead, they are now considered to be important mediators of intercellular regulation involved in various basic physiological and pathological processes
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In TME, EVs from different sources, including tumor cells, immune cells and other stromal cells, play different key roles in many aspects of tumor progression
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In this review, the author provides the latest insights into the biogenesis, excretion and uptake of EVS, and highlights the role of EVS in reshaping the tumor immune microenvironment (TIME)
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Finally, the limitations of current research and the direction of further research are discussed
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The tumor microenvironment is considered to be a complex environment, characterized by hypoxia, low pH, and nutrient deficiency.
Tumor cells often communicate with tumor-infiltrating immune cells to support tumor development
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Tumor microenvironmental stress has been shown to play a key role in tumor immune escape and tumor progression
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For example, microenvironmental acidosis can induce the initiation of a wide range of immune escape mechanisms.
Through this mechanism, tumor cells damage the anti-tumor activity of immune cells (including T cells, NK cells, and dendritic cells), and promote immunosuppressive cell sub-substances.
The accumulation and activation of groups, such as myeloid-derived suppressor cells and regulatory T cells, is conducive to tumor progression
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Many studies have shown that the delivery of tumor-inhibiting or activating molecular signals through extracellular vesicles can cause tumor-infiltrating immune cells to reprogram, allowing immune cells to play an important role in tumor progression
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Tumor-derived EVs recruit and induce immunosuppressive cells (including regulatory B cells (Breg), regulatory T cells (Treg), myeloid-derived suppressor cells (MDSCs), M2-like tumor-associated macrophages (TAMs) and medium The differentiation of sex granulocytes) to exert immunosuppressive activity.
These cells include regulatory B cells (Breg), regulatory T cells (Treg), myeloid-derived suppressor cells (MDSCs), and M2-like tumor-associated macrophages (TAMs) And neutrophils
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Tumor-derived EVs have been shown to regulate the tumor-promoting properties of Breg cells
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The extracellular high mobility group protein 1 (HMGB1) derived from hepatocellular carcinoma (HCC) can induce the proliferation of T cell immunoglobulin and mucin domain 1 (Tim-1) + Breg cells.
These cells secrete interleukin 10 (IL-10) and damage the function of CD8+ T cells to produce an immunosuppressive microenvironment
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Similarly, tumor-derived extracellular transforming growth factor β (tgf-β) participates in the expansion of treg cells from precursor cells in peripheral blood, and the expanded cells can produce transforming growth factor-β (tcf-β).
In turn, it exerts an inhibitory effect
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Myeloid-derived suppressor cells (MDSCs) are also activated by tumor-derived EVS
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An example is the 72 kDa heat shock protein (Hsp72), a tumor-derived extracellular surface protein, which can be triggered by Hsp72-Toll-like receptor 2 (TLR2) axis-mediated signal transducer and activator of transcription 3 (STAT3) activation The T cell-dependent immunosuppressive function of MDSCs
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In addition, tumor- derived exosomes can inhibit T cell proliferation and cytolysis mediated by transforming growth factor-β, allowing monocytes to differentiate into MDSCs
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The role of tumor extracellular vesicles in tumor immune microenvironment

Image source: https://doi.
org/10.
1016/j.
canlet.
2021.
05.
032

In recent decades, significant progress has been made in the understanding of the biology, function, and biomedical applications of extracellular vesicles, but further research is needed to completely solve the accurate classification of EV subtypes and clarify how these EVs are It plays multiple roles in tumor progression and tumor immunotherapy
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The selective sorting of EVS by source cells, the specific uptake of certain EVS by recipient cells, and the unique function of EV cargo in recipient cells seem to be the main determinants of the different functions of EVS at that time
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The research progress on the biogenesis, properties and active ingredients of different EV subgroups not only helps to understand the functional role of EV subgroups at the time, but also helps to identify clinical biomarkers and design drug interventions for the treatment of tumors
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Although people's interest in extracellular vesicles is increasing day by day, a way has been opened up for the use of extracellular bodies and extracellular bodies as clinical biomarkers, tumor vaccines and drug carriers , but challenges still remain
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It is unclear which cell types are suitable for the production of clinical-grade EVs
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In addition, there is an urgent need for large-scale EV purification, production and storage technologies
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The antigen or drug loading rate of EVS should also be increased to develop satisfactory EV vaccines and anti-tumor therapies
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In short, an in-depth understanding of the different roles of EVS in the tumor immune microenvironment and the development of methods to accurately design EVS will help EV anti- tumor therapy
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( Bioon.
com)

Reference

Pei-Pei Hou et al.
Extracellular vesicles in the tumor immune microenvironment.
Cancer Lett.
2021 May 31; 516: 48-56.
doi: 10.
1016/j.
canlet.
2021.
05.
032.