吲哚胺2,3-双加氧酶1改变急性髓系白血病微环境中B细胞亚群的比例。

IF 6.3 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yu Yao, Yu-Ying Liu, Jian-Feng Li, Yun-Shuo Chen, Lei Shi, Yang Shen, Li-Li Yang, Qing Yang
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引用次数: 0

摘要

急性髓性白血病(AML)是成人中最常见的白血病,具有与实体瘤相似的免疫逃逸特征。吲哚胺2,3-双加氧酶1 (IDO1)是一种公认的免疫检查点,已在AML母细胞中检测到表达,并与不良临床结果相关。虽然AML患者骨髓微环境中存在B细胞亚群失衡,但B细胞在AML中的作用及其与IDO1的相互作用尚不清楚。在此,通过生物信息学分析,我们发现IDO1表达与AML患者的生存和B细胞亚群比例密切相关。此外,我们对AML细胞和临床样本中IDO1的表达和活性、B细胞亚群比例和免疫抑制性白细胞介素-10 (IL-10)水平的研究显示了显著的结果。利用健康人PBMCs和AML细胞系的共培养系统,我们发现AML细胞中IDO1的高表达可以改变总B、调节性B和记忆性B细胞的比例,并增加IL-10的水平。最后,利用我们实验室设计的IDO1抑制剂RY103,我们发现IDO1抑制具有良好的抗白血病作用,可以恢复AML小鼠B细胞亚群的异常比例。我们的研究首次揭示了IDO1在AML中对B细胞亚群的调节,在理解AML的免疫逃逸机制方面取得了重大突破。应用IDO1抑制剂,如RY103,靶向B细胞亚群的失衡,可能导致AML的创新治疗。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Indoleamine 2,3-dioxygenase 1 alters the proportions of B cell subpopulations in the microenvironment of acute myeloid leukemia.

Acute myeloid leukemia (AML), the most common leukemia in adults, exhibits immune escape characteristics like solid tumors. The expression of indoleamine 2,3-dioxygenase 1 (IDO1), a well-recognized immune checkpoint, has been detected in AML blast cells and is associated with poor clinical outcome. Although an imbalance of B cell subpopulations exists in AML patients' bone marrow microenvironment, the role of B cells and their interaction with IDO1 in AML have yet to be elucidated. Herein, with bioinformatic analysis, we found the close correlations between IDO1 expression and survival and B cell subpopulation proportions in AML patients. Further, our investigation into IDO1 expression and activity, B cell subpopulation proportions and immunosuppressive interleukin-10 (IL-10) level in AML cells and clinical samples revealed significant findings. Using a co-culture system of healthy human PBMCs and AML cell lines, we demonstrated that high IDO1 expression in AML cells could alter the proportions of total B, regulatory B and memory B cells, and increased the level of IL-10. Finally, with the IDO1 inhibitor RY103 designed by our laboratory, we found that IDO1 inhibition had good anti-leukemic effect and restored the abnormal proportions of B cell subpopulations in AML mice. Our study is the first to reveal the modulation of IDO1 on B cell subpopulations in AML, making a significant breakthrough in understanding the immune escape mechanisms of AML. Application of IDO1 inhibitor, such as RY103, targeting the imbalance of B cell subpopulations can lead to innovative treatments for AML.

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CiteScore
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