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Review
. 2022 Jan 27;23(3):1461.
doi: 10.3390/ijms23031461.

Tumor-Derived Exosomes in Tumor-Induced Immune Suppression

Qiongyu Hao  1 , Yong Wu  1   2 , Yanyuan Wu  1   2 , Piwen Wang  1 , Jaydutt V Vadgama  1   2
Affiliations
Review

Tumor-Derived Exosomes in Tumor-Induced Immune Suppression

Qiongyu Hao et al. Int J Mol Sci. .

Abstract

Exosomes are a class of small membrane-bound extracellular vesicles released by almost all cell types and present in all body fluids. Based on the studies of exosome content and their interactions with recipient cells, exosomes are now thought to mediate "targeted" information transfer. Tumor-derived exosomes (TEX) carry a cargo of molecules different from that of normal cell-derived exosomes. TEX functions to mediate distinct biological effects such as receptor discharge and intercellular cross-talk. The immune system defenses, which may initially restrict tumor progression, are progressively blunted by the broad array of TEX molecules that activate suppressive pathways in different immune cells. Herein, we provide a review of the latest research progress on TEX in the context of tumor-mediated immune suppression and discuss the potential as well as challenges of TEX as a target of immunotherapy.

Keywords: immune suppression; tumor microenvironment; tumor-derived exosomes.

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Conflict of interest statement

The authors declare no potential conflict of interest.

Figures

Figure 1
Figure 1
Machinery involved in the biogenesis of extracellular vesicles. Sorting machineries for generating exosomes and microvesicles requires different steps. Membrane-associated proteins and lipids are clustered in discrete membrane microdomains of the multivesicular endosome (MVE) limiting membrane for exosomes. Such microdomains certainly recruit the soluble components, such as extracellular proteins and RNA species by endocytosis. The ESCRT machinery acts in a stepwise manner. ESCRT0 ubiquitylated trans-membrane cargoes on microdomains of MVBs, and ESCRTI subunits cluster, then the soluble components, such as cytosolic proteins and RNA species fating for sorting were recruited via ESCRTII and the ESCRTIII sub-complexes that perform budding and fission. The late endosome MVBs will fuse with the plasma membrane to release the ILVs into the extracellular environment as exosomes by exocytosis.
Figure 2
Figure 2
Molecular composition and genetic profiles of TEX. The presence of immune-inhibitory molecules has been confirmed on the TEX surface. The intravesicular molecular composition of TEX is composed of protein (enzymes, signal transducer, biogenesis factors, chaperones, and so on) and nucleic acid (mRNA, miRNA, long non-coding RNA, circRNA, DNA).
Figure 3
Figure 3
Tumor-released exosomes and their implications in cancer immunity. TEX-mediated signals interfere with immune cell functions at multiple levels and summarize various molecular mechanisms responsible for TEX-mediated effects. The communication network is entirely tumor-driven and designed to promote tumor progression and metastasis by silencing antitumor immune responses.
See this image and copyright information in PMC

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