Regulation of Antitumor Immune Responses by Exosomes Derived from Tumor and Immune Cells

Abstract

Exosomes are lipid membrane-enclosed vesicles released by all cell types that act at the paracrine or endocrine level to favor cell differentiation, tissue homeostasis, organ remodeling and immune regulation. Their biosynthesis begins with a cell membrane invagination which generates an early endosome that matures to a late endosome. By inward budding of the late endosome membrane, a multivesicular body (MVB) with intraluminal vesicles (ILVs) is generated. The fusion of MVBs with the plasma membrane releases ILVs into the extracellular space as exosomes, ranging in size from 30 to 100 nm in diameter. The bilipid exosome membrane is rich in cholesterol, ceramides and phosphatidylserine and can be loaded with DNA, RNA, microRNAs, proteins and lipids. It has been demonstrated that exosome secretion is a common mechanism used by the tumor to generate an immunosuppressive microenvironment that favors cancer development and progression, allowing tumor escape from immune control. Due to their ability to transport proteins, lipids and nucleic acids from the cell that gave rise to them, exosomes can be used as a source of biomarkers with great potential for clinical applications in diagnostic, prognostic or therapeutic areas. This article will review the latest research findings on exosomes and their contribution to cancer development.

The emerging roles of exosomal long non‐coding RNAs in bladder cancer

“…69,70 Mast cells transport their mRNA and miRNA to recipient cells through the released exosomes, and translate proteins in the recipient cells, thus proving that exosomes have the function of transporting substances. 71,72 The lipid bilayer membrane of exosomes reduces the degradation of exosomes by proteases and ribonuclease, and is shed from the cell membrane through autocrine, paracrine and endocrine secretion pathways. [73][74][75] The membrane carries proteins and nucleic acid signal molecules.…”

Advanced and Innovative Nano-Systems for Anticancer Targeted Drug Delivery

“…Exosomes are naive extracellular vesicles, ranging in size from 40 to 100 nm, which are generated by all types of pro- and eukaryotic cells in the way of inward budding of the plasma membrane [ 151 ]. Structurally, exosomes are composed of a lipid bilayer to carry both hydrophobic and hydrophilic drugs [ 152 ] ( Figure 7 A,B).…”

Bladder Cancer Extracellular Vesicles Elicit a CD8 T Cell-Mediated Antitumor Immunity

“…While initially disregarded as a form of cellular garbage, in the late 1990s, it was discovered that EVs could play a variety of functional roles in the physiology and pathophysiology of different diseases, including cardiovascular diseases, diabetes and cancer. Accumulating evidence indicated that tumor-derived EVs (TEVs) play an integral role in all stages of cancer progression, functioning to promote neoplastic transformation, cancer cell survival, metastasis, angiogenesis and immune suppression [ 3 , 4 , 5 , 6 , 7 , 8 ]. In contrast, fewer studies have explored the roles of EVs as modulators of antitumor immune responses, and this topic remains understudied in the context of bladder cancer (BC).…”