Engineered Tumor-Derived Extracellular Vesicles: Potentials in Cancer Immunotherapy

Abstract

Exosomes are nano vesicles from the larger family named Extracellular Vesicle (EV)s which are released by various cells including tumor cells, mast cells, dendritic cells, B lymphocytes, neurons, adipocytes, endothelial cells, and epithelial cells. They are considerable messengers that can exchange proteins and genetic materials between the cells. Within the past decade, Tumor derived exosomes (TEX) have been emerged as important mediators in cancer initiation, progression and metastasis as well as host immune suppression and drug resistance. Although tumor derived exosomes consist of tumor antigens and several Heat Shock Proteins such as HSP70 and HSP90 to stimulate immune response against tumor cells, they contain inhibitory molecules like Fas ligand (Fas-L), Transforming Growth Factor Beta (TGF-β) and Prostaglandin E2 (PGE2) leading to decrease the cytotoxicity and establish immunosuppressive tumor microenvironment (TME). To bypass this problem and enhance immune response, some macromolecules such as miRNAs, HSPs and activatory ligands have been recognized as potent immune inducers that could be used as anti-tumor agents to construct a nano sized tumor vaccine. Here, we discussed emerging engineered exosomes as a novel therapeutic strategy and considered the associated challenges.

Extracellular Vesicles as Biomarkers in Cancer Immunotherapy

“…TDEs can carry immunosuppressive molecules such as PD-L1, TGFβ1, FasL, TRAIL, and NKG2D ligands which make them important mediators of tumor immune evasion and possible targets for immunotherapy [ 63 , 64 , 65 , 66 , 67 ]. Metastatic melanoma-derived exosomes, which are stimulated by interferon-γ (IFN-γ), expressed more PD-L1 on these vesicles and inhibited antitumor responses [ 31 ].…”

Role of Chronic Lymphocytic Leukemia (CLL)-Derived Exosomes in Tumor Progression and Survival

“…The composition of exosomal cargo depends on the parental cell with a high heterogeneity among all circulating exosomes. Exosomes can transport nucleic acids, (e.g., DNA, mRNA, miRNA), proteins (e.g., tetraspanins, heat shock proteins), lipids (e.g., cholesterol, sphingomyelin, ceramide), and Fas ligands [41][42][43]. Several proteins, such as CD63, CD81, CD9, TSG-101, Syndecan-1, MHC molecules, ALIX, HSP70 and BCR, are located on the surface of exosomes or included as cargo of exosomes and may represent markers of the paternal cell [44][45][46][47][48].…”

Extracellular Vesicles in the Tumour Microenvironment: Eclectic Supervisors

“…A number of studies have suggested that EV within the TME act as central mediators of angiogenesis, immune modulation, and metastatic spread [14]. This implies that EV can be considered to be potential targets for a new generation of pharmaceuticals directed at reprogramming the TME [15,16]. Herein, the most relevant pro-tumour actions of EV released from different cell types in the TME are examined.…”