Abstract

Simple SummaryCancer is a lethal disease and the second most common cause of death worldwide. It is estimated that the next decades will bring a rise of about 50% in cancer incidence and mortality. At present, immunotherapy has shown the best results for cancer treatment. Because of this, the study of the anti-tumor immune response has gained a significant importance in cancer research. Many are the factors described to be involved in this process. Exosomes are extracellular vesicles that shape the cellular program of the recipient cells and are involved in cancer progression. Our review explores the link between exosomes and natural killer (NK) cells, the possible consequences in cancer progression, and the enclosed potential to identify new immunotherapy targets within this crosstalk.Natural killer (NK) cells are innate lymphoid cells involved in tumor surveillance. These immune cells have the potential to fight cancer growth and metastasis, as such, their deregulation can result in tumor immune escape. Recently exosomes were described as mediators of intercellular communication between cancer and NK cells. The exact role of this subclass of extracellular vesicles (EVs), which transport genetic and molecular material to recipient cells, in NK cell biology in the context of cancer, is still an open question. Several reports have demonstrated that tumor-derived exosomes (TDEs) can exert immunomodulatory activities, including immunosuppression, thus promoting cancer progression. Some reports demonstrate that the interplay between cancer exosomes and NK cells allows tumors to escape immune regulation. On the other hand, tumor exosomes were also described to activate NK cells. Additionally, studies show that NK cell exosomes can modulate the immune system, opening up their potential as an immunotherapeutic strategy for cancer treatment. Our review will focus on the reprogramming effect of cancer exosomes on NK cells, and the immunotherapeutic potential of NK cells-derived exosomes.

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