The emerging role of exosome and microvesicle- (EMV-) based cancer therapeutics and immunotherapy

Abstract

There is an urgent need to develop new combination therapies beyond existing surgery, radio- and chemo-therapy, perhaps initially combining chemotherapy with the targeting specificities of immunotherapy. For this, strategies to limit inflammation and immunosuppression and evasion in the tumour microenvironment are also needed. To devise effective new immunotherapies we must first understand tumour immunology, including the roles of T cells, macrophages, myeloid suppressor cells and of exosomes and microvesicles (EMVs) in promoting angiogenesis, tumour growth, drug resistance and metastasis. One promising cancer immunotherapy discussed uses cationic liposomes carrying tumour RNA (RNA-lipoplexes) to provoke a strong anti-viral-like (cytotoxic CD8 ) anti-tumour immune response. Mesenchymal stem cell-derived EMVs, with their capacity to migrate towards inflammatory areas including solid tumours, have also been used. As tumour EMVs clearly exacerbate the tumour microenvironment, another therapy option could involve EMV removal. Affinity-based methods to deplete EMVs, including an immunodepletion, antibody-based affinity substrate, are therefore considered. Finally EMV and exosome-mimetic nanovesicles (NVs) delivery of siRNA or chemotherapeutic drugs that target tumours using peptide ligands for cognate receptors on the tumour cells are discussed. We also touch upon the reversal of drug efflux in EMVs from cancer cells which can sensitize cells to chemotherapy. The use of immunotherapy in combination with the advent of EMVs provides potent therapies to various cancers.

Tumor-Secreted Exosomal miR-222 Promotes Tumor Progression via Regulating P27 Expression and Re-Localization in Pancreatic Cancer

“…Exosomes were first identified in mammalian reticulocytes, but their presence has been confirmed in different tumor cells; they can transfer a wide variety of biological components, including proteins, miRNAs, mRNAs, lncRNA and circular RNAs, to other recipient cells via cellular communication [18,19]. Recently, more and more studies have shown that tumor exosomes play key roles in cell communication, the immune system and tumor invasion.…”

Tumoral microvesicle–activated glycometabolic reprogramming in fibroblasts promotes the progression of oral squamous cell carcinoma

“…Loss of stromal CAV1 was associated with CAF activation and predicted poor clinical outcome (23). The critical role of EVs in tumor‐stroma interaction and the fact that glycometabolic reprogramming is an important aspect of tumor‐stroma interaction (2, 13) raise the question of whether a relationship exists between EVs and metabolic reprogramming in cancers. In addition, tumor microenvironment–derived vesicles were capable of modulating cancer cell metabolism and promoting tumor progression (24, 25).…”

Patient monitoring through liquid biopsies using circulating tumor DNA

“…As the field is so rapidly evolving, review articles on this topic are being published almost on a weekly basis. Here, we list just a few recent comprehensive reviews, which were published on CTCs, 6-12 ctDNA, 7,10,11,[13][14][15][16][17][18][19] and exosomes or extracellular vesicles, respectively, 14,[20][21][22] and which covered most relevant aspects of these relatively novel technologies.…”