Leukemic cells facilitate the creation of the tumor-favorable microenvironment in the bone marrow niche using their secreted factors. There are not comprehensive details about immunosuppressive properties of chronic myelogenous leukemia-derived exosomes in the bone marrow stromal and immune compartment. We explained here that K562-derived exosomes could affect the gene expression, cytokine secretion, nitric oxide (NO) production, and redox potential of human primary cord blood-derived T cells (CB T cells). Human primary cord blood-derived T cells were treated with K562-derived exosomes. We evaluated the expression variation of some critical genes activated in suppressor T cells. The alterations of some inflammatory and anti-inflammatory cytokines levels were assessed using ELISA assay and real-time PCR. Finally, NO production and intracellular ROS level in CB T cells were evaluated using Greiss assay and flow cytometry, respectively. Our results showed the over-expression of the genes involved in inhibitory T cells, including NQO1, PD1, and FoxP3. In contrast, genes involved in T cell activation such as CD3d and NFATc3 have been reduced significantly. Also, the expression of interleukin 10 (IL-10) and interleukin 6 (IL-6) mRNAs were significantly up-regulated in these cells upon exosome treatment. In addition, secretion of the interleukin 10, interleukin 6, and interleukin 17 (IL-17) proteins increased in T cells exposed to K562-derived exosomes. Finally, K562-derived exosomes induce significant changes in the NO production and intracellular ROS levels in CB T cells. These results demonstrate that K562-derived exosomes stimulate the immunosuppressive properties in CB-derived T cells by inducing anti-inflammatory cytokines such as IL-10, reducting ROS levels, and arising of NO synthesis in these cells. Moreover, considering the elevation of FOXP3, IL-6, and IL-17 levels in these cells, exosomes secreted by CML cells may induce the fates of T cells toward tumor favorable T cells instead of conventional activated T cells.

中文翻译：

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CML衍生的外泌体在T细胞中促进肿瘤有利的功能表现

白血病细胞利用其分泌因子促进在骨髓生态位中创造有利于肿瘤的微环境。没有关于骨髓基质和免疫区室中慢性粒细胞白血病衍生的外泌体的免疫抑制特性的全面细节。我们在这里解释说，K562 衍生的外泌体可以影响人类原代脐带血衍生 T 细胞（CB T 细胞）的基因表达、细胞因子分泌、一氧化氮 (NO) 产生和氧化还原电位。用 K562 衍生的外泌体处理人原代脐带血衍生的 T 细胞。我们评估了抑制性 T 细胞中激活的一些关键基因的表达变异。使用ELISA测定和实时PCR评估了一些炎症和抗炎细胞因子水平的改变。最后，分别使用 Greiss 测定和流式细胞术评估 CB T 细胞中的 NO 产生和细胞内 ROS 水平。我们的结果显示抑制性 T 细胞中涉及的基因过度表达，包括 NQO1、PD1 和 FoxP3。相比之下，参与 T 细胞活化的基因，如 CD3d 和 NFATc3，已显着减少。此外，外泌体处理后，这些细胞中白介素 10 (IL-10) 和白介素 6 (IL-6) mRNA 的表达显着上调。此外，在暴露于 K562 衍生外泌体的 T 细胞中，白介素 10、白介素 6 和白介素 17 (IL-17) 蛋白的分泌增加。最后，K562 衍生的外泌体诱导 CB T 细胞中 NO 产生和细胞内 ROS 水平的显着变化。这些结果表明，K562 衍生的外泌体通过诱导抗炎细胞因子（如 IL-10）、降低 ROS 水平和在这些细胞中产生 NO 合成来刺激 CB 衍生的 T 细胞的免疫抑制特性。此外，考虑到这些细胞中 FOXP3、IL-6 和 IL-17 水平的升高，CML 细胞分泌的外泌体可能会诱导 T 细胞向肿瘤有利 T 细胞而不是常规活化 T 细胞的命运。