Exosomes in cancer theranostic: Diamonds in the rough

Abstract

During the last 10 years, exosomes, which are small vesicles of 50-200 nm diameter of endosomal origin, have aroused a great interest in the scientific and clinical community for their roles in intercellular communication in almost all physiological and pathological processes. Most cells can potentially release these nanovesicles that share with the parent cell a similar lipid bilayer with transmembrane proteins and a panel of enclosed soluble proteins such as heat shock proteins and genetic material, thus acting as potential nanoshuttles of biomarkers. Exosomes surface proteins allow their targeting and capture by recipient cells, while the exosomes' content can modify the physiological state of recipient cells. Tumor derived exosomes by interacting with other cells of the tumor microenvironment modulate tumor progression, angiogenic switch, metastasis, and immune escape. Targeting tumor-derived exosomes might be an interesting approach in cancer therapy. Furthermore, because a key issue to improve cancer patients' outcome relies on earlier cancer diagnosis (metastases, as opposed to the primary tumor, are responsible for most cancer deaths) exosomes have been put forward as promising biomarker candidates for cancer diagnosis and prognosis. This review summarizes the roles of exosomes in cancer and clinical interest, focusing on the importance of exosomal heat shock proteins (HSP). The challenges of clinical translation of HSPexosomes as therapeutic targets and biomarkers for early cancer detection are also discussed.

Recent advances in exosome-based cancer immunotherapy.

“…Exosomes are cell-derived lipid extracellular vesicles (EVs) with a diameter of 50-200 nm and a density of 1.13-1.19 g/ml, playing important roles in intercellular communication and biomolecule transmission, where donor cells secrete exosomes for the delivery of various biological elements to recipient cells ( Figure 2A) [1,14]. Exosomes contain lipids, nucleic acids and proteins ( Figure 2B), which vary with the type of the donor cell.…”

“…According to the exosome data base, ExoCarta (http:// exocarta.org/index.html), more than 1116 lipid entries, 2838 miRNAs, 3408 mRNAs and 9769 proteins have been characterized in exosomes. In the exosomal lipid-bilayer structure, lipid materials like ceramide, cholesterol, sphingomyelin and phospholipid have been reported [1,15]. In addition to lipids, exosomes contain DNA, mRNA and miRNA, which may mediate cellular information transfer.…”

“…Exosomes have a similar vesicle structure as liposomes, an artificial lipid-bilayer nanodelivery system, which has already been successfully employed for immunotherapy of cancer [46,47]. In addition, the endogenous origin and loaded biological materials of exosomes endow them with superior power for the delivery of immunological regulators under various physiological and pathological conditions, such as good biocompatibility, nonimmunogenicity, natural targeting and high penetration of biological barriers [1,17,48,49]. Mahmoodzadeh et al decorated MDA MB-231 cancer cell exosomes with staphylococcal enterotoxin B, a bacterial superantigen that binds to MHC II and polyclonally activates T cells, which achieved apoptosis in esterogen receptor-negative (ER-) breast cancer cells [50,51].…”

“…Following the discovery of their immunological functions in 1996, exosomes have been re-classified from inconsequential cell garbage boxes to critical players in cell-cell communication [1][2][3]. Since then, extensive attention has been drawn to exosomes, resulting in a dramatic rise in publication numbers (Figure 1), and the initiation of clinical trials involving exosomes [4,5].…”

“…concentration, composition) are cancer-dependent, for instance, the increased number in body fluids of cancer patients [11]. Inspired by these discoveries, exosomes have been explored and tested for cancer immunotherapy [1,8,12,13]. This review covers the current understanding of exosomes in composition, isolation and characterization, and highlights the state of the art of exosomebased cancer immunotherapy, including exosomal carriers, exosome-based immune regulators and engineered exosomes, with a discussion on challenges and future perspectives.…”