Immune Modulation By Tumor Derived Exosomes: Role Of Engineering In Immune Stimulation

Exosomes are nano vesicles and member of the larger family named Extracellular Vesicles which arereleased by any kind of cells such as immune cells and tumor cells. They are considerablemessengers that can exchange proteins and genetic materials between the cells. Within the pastdecade, Tumor derived Exosomes (TEX) have been emerged as important mediators in cancerinitiation, progression and metastasis as well as host immune suppression and drug resistance.Furthermore we performed a systematic search with combining the key words ‘Tumor derivedexosomes’, Immune suppression’ and ‘Exosome Engineering’ on Google scholar, Scopus, and ISI fromEnglish articles which studied on tumor derived exosomes and their immune function. Referring torecent progresses in understanding the role of exosome in immune suppression, tumor derivedexosomes are being involved in the transmission of signals between tumor cells and immune cells(Dendritic cells, Natural Killer cells, CD4+ and CD8+ T cells, etc.) through which the efficiencyagainst tumor antigens would decrease and consequently the regulatory responses mediated by Tregulatories and Myeloid-derived Suppressor Cell (MDSCs) would increase. Although tumorderived exosomes consist of tumor antigens and several Heat Shock Proteins such as HSP70 andHSP90 to induce immunity against tumor cells, they contain inhibitory molecules like Fas ligand(Fas-L), Transforming Growth Factor Beta (TGF-β) and Prostaglandin E2 (PGE2) leading to decreasethe cytotoxicity and promote the regulatory effects. As mentioned above, TEX have some potentialmolecules which are beneficial themselves but the inhibitory molecules overcome the tumorantigens and HSPs. Some macromolecules such as miRNAs, HSPs and activatory ligands have beenrecognized as potent immune inducers that could be used as agents to construct a TEX based tumorvaccine. Here, we discussed emerging engineered exosomes as a novel therapeutic agent andconsidered the associated challenges. It is also necessary to gather research data from engineeredexosomes to assess their effectiveness in immune induction In vitro and In vivo.