胞外囊泡（EV）是肿瘤微环境中自然杀伤细胞活性（NKA）的重要调节因子。外周血循环中的EV和前列腺癌患者自然杀伤（NK）细胞之间的关系尚不清楚。该研究旨在调查前列腺癌患者术前和术后循环EV和NK细胞相互作用中的关键调节因子。 NK细胞特征在79名接受机器人辅助腹腔镜下根治前列腺切除术（RARP）治疗的患者中进行前瞻性评估。与健康供体相比，前列腺肿瘤的存在增加了循环EV的数量并改变了EV的配体表达。从癌症患者中提取的循环EV与从健康供体中提取的EV相比，显著降低了NK细胞的NKA水平。在使用抑制抗体或小干扰RNA（siRNA）治疗后，自然杀伤细胞蛋白组2A（NKG2A）被确定为癌症患者中接受循环EV信号的主要NKA调节因子。手术后，NKA增加，NK细胞上的NKG2A表达显著降低。 NKG2D配体的表达和循环EV的水平都显著增加。随着NK细胞上NKG2A水平的降低以及循环EV中NKG2D配体总数的增加，NKG2A和循环外泌体中NKG2D配体都是前列腺切除术后NKA恢复的主要调节因子。本文受版权保护。保留所有权利。

Extracellular vesicles (EVs) are an important regulatory factor for natural killer cell activity (NKA) in the tumor microenvironment. The relationship between circulating EVs in the peripheral blood and natural killer (NK) cells in prostate cancer is unclear. This study aims to investigate the key regulators in the interaction between circulating EVs and NK cells in prostate cancer patients before and after tumor removal. NK-cell characteristics were prospectively assessed in 79 patients treated with robot-assisted laparoscopic radical prostatectomy (RARP) preoperatively and postoperatively. Compared with healthy donors, the existence of prostate tumors increased the number of circulating EVs and altered ligand expression of EVs. Circulating EVs extracted from cancer patients significantly decreased NKA of NK cells compared to those extracted from healthy donors. Upon treatment with an inhibiting antibody or small interfering RNA (siRNA), natural killer cell protein group 2A (NKG2A) was identified as the main NKA regulator in cancer patients for accepting the signal from circulating EVs. 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. With the decrease in NKG2A levels on NK cells and the increase in total NKG2D ligands on circulating EVs, which was increased postoperatively, both NKG2A on NK cells and NKG2D ligands on circulating exosomes are main regulators of NKA restoration after prostatectomy.This article is protected by copyright. All rights reserved.