外泌体能有效调节肿瘤微环境中癌细胞与正常细胞之间的相互作用。通过其携带的分子，它们还能调节癌细胞的增殖和凋亡。通过透射电子显微镜（TEM）和差速超离心法，我们验证了外泌体的存在。通过体内和体外实验，我们确定了外泌体循环_001264在急性髓系白血病（AML）细胞与M2型巨噬细胞之间相互作用调控机制。RNA pull-down和双荧光素酶报告基因实验帮助我们进一步分类了外泌体循环_001264介导的机制。此外，我们采用可编程死亡配体1抗体（aPD-L1）与外泌体循环_001264 siRNA联合用于体外抗肿瘤治疗，采用体内小鼠模型验证了体内结果。我们的研究揭示了AML患者中外泌体循环_001264过度表达的异常情况，以及其与患者预后不良的相关性。AML细胞来源的外泌体循环_001264调节了RAF1的表达，并激活了p38-STAT3信号通路，从而诱导了M2型巨噬细胞的极化。极化的M2型巨噬细胞可以通过分泌PD-L1诱导其过表达。为了预防免疫抑制，我们采用编程性死亡配体1（aPD-L1），它能够在肿瘤部位达到预期的治疗效果。事实上，在小鼠模型中，外泌体循环_001264 siRNA加上aPD-L1联合组的白血病肿瘤负荷明显减少。总的来说，我们的研究为AML治疗提供了理论依据。外泌体循环_001264 siRNA和aPD-L1联合给予在AML中表现出明显的抗癌效果。版权所有 © 2023 Elsevier B.V.。保留所有权利。

Exosomes can help to effectively regulate the crosstalk between cancer cells and normal cells in the tumor microenvironment. They also regulate cancer cell proliferation and apoptosis by virtue of their cargo molecules. Transmission electron microscopy (TEM) together with differential ultracentrifugation served for verifying the presence of exosomes. In vivo and in vitro assays served for determining the role of exosomal circ_001264. RNA pull-down and dual-luciferase reporter assays assisted in the classification of the mechanism of exosomal circ_001264-mediated regulation of the crosstalk between Acute myeloid leukemia (AML) cells and M2 macrophages. Furthermore, we adopted a programmed death ligand 1 antibody (aPD-L1) in combination with exosomal circ_001264 siRNA for antitumor treatment in vitro and in vivo mouse models served for validating the in vivo outcomes. Out study illustrated the aberrant overexpression of circ_001264 in AML patients and its correlation with poor patient prognosis. AML cell-derived exosomal circ_001264 regulated the RAF1 expression and activated the p38-STAT3 signaling pathway, thereby inducing the M2 macrophage polarization. Polarized M2 macrophages can induce PD-L1 overexpression by secreting PD-L1. Here, a programmed death ligand (aPD-L1) was adopted for preventing the immunosuppression, which was able to achieve the desired therapeutic effect at the tumor site. Indeed, in the mouse model, leukemia tumor load decreased remarkably in the exosomal circ_001264 siRNA plus aPD-L1 combination group. Taken together, our study contributed to a theoretical basis for AML treatment. The co-administration of exosomal circ_001264 siRNA and aPD-L1 exhibited an obvious anti-cancer effectiveness in AML.Copyright © 2023 Elsevier B.V. All rights reserved.