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Extracellular vesicles (EVs) play a crucial role in regulating natural killer cell activity (NKA) in the tumor microenvironment. The study aimed to investigate the regulators in the interaction between circulating EVs and NK cells in prostate cancer patients before and after tumor removal. The existence of prostate tumors increased the number of circulating EVs and altered ligand expression of EVs. NKG2A was identified as the main NKA regulator in cancer patients. After surgery, NKA was increased, and NKG2A expression on NK cells was significantly reduced. The expression of ligands for NKG2D on EVs and the level of circulation EVs both significantly increased. Both NKG2A on NK cells and NKG2D ligands on circulating exosomes are the main regulators of NKA restoration after prostatectomy.
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