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急性髓系白血病中吲哚胺2,3-双加氧酶表达增加及调节性T细胞:对免疫逃逸和治疗靶点的影响

Increased IDO expression and regulatory T cells in acute myeloid leukemia: implications for immune escape and therapeutic targeting.

作者信息

Hakak Raziyeh, Poopak Behzad, Majd Ahmad

机构信息

Department of Cellular and Molecular Biology, Faculty of Biological Sciences, North Tehran Branch, Islamic Azad University, Tehran, Iran.

Payvand Clinical and Specialty Laboratory, Tehran, Iran.

出版信息

Blood Res. 2024 Dec 18;59(1):42. doi: 10.1007/s44313-024-00048-0.

Abstract

PURPOSE

This study aimed to determine the frequency of regulatory T cells (Tregs) (CD4/FOXP3) and indoleamine 2,3-dioxygenase (IDO) expression in patients with acute myeloid leukemia (AML).

METHODS

This cross-sectional case-control study was conducted between Jan 2022 and Dec 2023. Bone marrow samples were collected from 20 healthy individuals and 15 patients with AML. Flow cytometry, real-time polymerase chain reaction (PCR), and western blotting were used to evaluate the frequency of Treg and IDO expression levels.

RESULTS

The Treg percentage among total lymphocytes was lower in the AML group than that in the normal group. However, Treg percentage among T-helper (Th) lymphocytes was significantly higher in the AML group than that in the normal group (p < 0.05). The mean IDO expression in the AML group was significantly higher than that in the normal group (p = 0.004). A significant relationship was observed between IDO expression and Treg percentage among Th lymphocytes in the AML group (correlation = 0.637; p = 0.003). Moreover, western blot analysis showed a significant increase in IDO protein intensity in the AML group compared with that in the control group (p < 0.001). A significant difference was observed between the IDO concentrations in the AML group and that in the control group (p < 0.001). In addition, a significant difference between TGF-β levels in the AML group and those in the control group (p < 0.01) was observed.

CONCLUSION

IDO inhibition using novel IDO inhibitors along with chemotherapy is a promising approach to overcome the immune escape mechanisms in patients with AML, who exhibit increased levels of IDO expression and Tregs.

摘要

目的

本研究旨在确定急性髓系白血病(AML)患者中调节性T细胞(Tregs,CD4/FOXP3)的频率以及吲哚胺2,3-双加氧酶(IDO)的表达情况。

方法

本横断面病例对照研究于2022年1月至2023年12月进行。从20名健康个体和15名AML患者中采集骨髓样本。采用流式细胞术、实时聚合酶链反应(PCR)和蛋白质印迹法评估Treg频率和IDO表达水平。

结果

AML组总淋巴细胞中Treg百分比低于正常组。然而,AML组辅助性T细胞(Th)中Treg百分比显著高于正常组(p < 0.05)。AML组IDO平均表达显著高于正常组(p = 0.004)。在AML组中,观察到IDO表达与Th淋巴细胞中Treg百分比之间存在显著相关性(相关性 = 0.637;p = 0.003)。此外,蛋白质印迹分析显示,与对照组相比,AML组IDO蛋白强度显著增加(p < 0.001)。AML组与对照组之间IDO浓度存在显著差异(p < 0.001)。此外,还观察到AML组与对照组之间转化生长因子-β水平存在显著差异(p < 0.01)。

结论

使用新型IDO抑制剂联合化疗抑制IDO是一种有前景的方法,可克服AML患者的免疫逃逸机制,这些患者表现出IDO表达水平和Tregs增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ace0/11655893/792ec191f682/44313_2024_48_Fig1_HTML.jpg

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