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在急性髓性白血病中,STAT5促进PD-L1表达,通过促进基因素乳化来驱动免疫抑制,从而促进PD-L1表达

Ze-Wei Huang¹, Xue-Ning Zhang¹, Ling Zhang¹

¹Department of Hematology, The Third Affiliated Hospital, Sun Yat-sen University; Institute of Hematology, Sun Yat-sen University, Guangzhou, China.

Signal transduction and targeted therapy

|September 30, 2023

概括

在急性髓性白血病 (AML) 细胞中,STAT5激活促进糖解和乳酸盐的产生,导致PD-L1的表达. 这种STAT5-乳酸盐-PD-L1网络表明,高STAT5的AML患者可能受益于PD-1/PD-L1免疫疗法.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
代谢途径代谢途径

背景情况:

免疫疗法,特别是免疫检查点抑制剂 (ICI),在各种癌症中表现有前途,包括血液恶性瘤.
急性髓性白血病 (AML) 是一种复杂的疾病,PD-1/PD-L1阻断性免疫治疗的成功程度有限.
在AML中确定免疫疗法分层的新目标至关重要.

研究的目的:

阐明驱动AML免疫抑制的分子机制.
确定用于预测AML患者对PD-1/PD-L1抑制剂的反应的生物标志物.
研究STAT5在AML进展和免疫逃避中的作用.

主要方法:

在AML患者队列中分析STAT5表达.
调查STAT5对糖溶性基因促进体的影响.
测量乳酸积累和基因素乳酸化.
评估PD-L1转录及其调节.
评估ICI在共同培养模型中的有效性.
将临床数据与分子发现相关联.

主要成果:

在AML中STAT5的表达很高,并促进糖解,增加乳酸水平.
乳酸盐的积累促进了组织素的乳糖化,并增强了PD-L1转录.
在STAT5激活的AML模型中,PD-1/PD-L1阻塞可以破坏T细胞相互作用.
临床数据显示,AML患者的骨髓乳酸,STAT5和PD-L1表达之间存在正相关性.

结论:

在AML进展中发现了一种新的STAT5-乳酸盐-PD-L1轴.
STAT5驱动的糖解和乳酸积累有助于AML的免疫逃避.
高STAT5和相关代谢变化的AML患者可能受益于PD-1/PD-L1基础的免疫疗法.

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