Systemic immunosuppression greatly affects the chemotherapeutic antitumor effect. Here, we showed that CD19⁺ extracellular vesicles (EVs) from B cells through CD39 and CD73 vesicle-incorporated proteins hydrolyzed ATP from chemotherapy-treated tumor cells into adenosine, thus impairing CD8⁺ T cell responses. Serum CD19⁺ EVs were increased in tumor-bearing mice and patients. Patients with fewer serum CD19⁺ EVs had a better prognosis after chemotherapy. Upregulated hypoxia-inducible factor-1α (HIF-1α) promoted B cells to release CD19⁺ EVs by inducing Rab27a mRNA transcription. Rab27a or HIF-1α deficiency in B cells inhibited CD19⁺ EV production and improved the chemotherapeutic antitumor effect. Silencing of Rab27a in B cells by inactivated Epstein-Barr viruses carrying Rab27a siRNA greatly improved chemotherapeutic efficacy in humanized immunocompromised NOD Prkdc^scid Il2rg^−/− mice. Thus, decreasing CD19⁺ EVs holds high potential to improve the chemotherapeutic antitumor effect.

全身免疫抑制极大地影响化学疗法的抗肿瘤作用。在这里，我们显示了B细胞通过CD39和CD73囊泡结合的CD19 ⁺细胞外囊泡（EVs）将ATP从化疗后的肿瘤细胞中水解为腺苷，从而削弱了CD8 ⁺ T细胞的反应。荷瘤小鼠和患者的血清CD19 ⁺ EV升高。血清CD19 ⁺ EV较少的患者在化疗后预后较好。缺氧诱导因子-1α（HIF-1α）上调通过诱导Rab27a mRNA转录促进B细胞释放CD19 ⁺ EV 。B细胞中Rab27a或HIF-1α缺乏抑制CD19 ⁺电动汽车的生产和改善了化学疗法的抗肿瘤作用。通过进行灭活爱泼斯坦-巴尔病毒的B细胞的Rab27a沉默Rab27a的siRNA大大提高化疗的功效在人源化免疫受损NOD PRKDC ^SCID 的II2rg ^{/ - -}小鼠。因此，减少CD19 ⁺ EVs具有提高化疗抗肿瘤作用的高潜力。