AML中的免疫代谢可塑性：活化细胞毒性T细胞（aCTLs）和犬尿氨酸的预后作用

摘要(中文译文)

急性髓系白血病（AML）传统上依据遗传学异常进行风险分层，是一种侵袭性恶性肿瘤，复发率高且生存率有限。免疫失调是一种新兴的致病机制。我们研究了78例新诊断的成人AML患者（均接受统一强化治疗）的细胞免疫亚群以及PD-L1/PD-1和IDO1-犬尿氨酸-AhR通路的代谢介质，包括作为免疫调节成分的维生素D。较低的TLC（<30 × 10⁹/L）和原始细胞比例（<67%）与较高的CR率相关（OR=3.9，p=0.006；OR=2.9，p=0.025）。较高的基线活化细胞毒性T细胞（aCTL；CD8+ PLCγ1+）预示更好的OS（18个月OS 60.9% vs. 32.2%；p=0.023）。其他基线临床、维生素D和免疫参数与OS或LFS无关。诱导治疗后，犬尿氨酸和Treg/CTL比值升高，而色氨酸、aCTL和aTreg/aCTL比值降低。较高的治疗后犬尿氨酸与更好的OS（30% vs. 64%；p=0.017）和LFS（44% vs. 71%；p=0.09）相关。这些发现凸显了AML中复杂且可塑的免疫相互作用，具有潜在的预后和治疗意义。微型摘要：这项针对初诊急性髓系白血病（AML）的研究表明，较高的基线活化细胞毒性T细胞（CD8+PLCγ1+）和诱导后犬尿氨酸升高是与强化化疗后生存改善相关的新型预后标志物。化疗治疗诱导了动态的免疫代谢变化，强调了将免疫分析整合到AML临床管理中的重要性。

Abstract

Acute myeloid leukemia (AML), traditionally risk-stratified by genetic abnormalities, is an aggressive malignancy with high relapse and modest survival. Immune dysregulation is an emerging pathogenic mechanism. We investigated cellular immune subsets and metabolic mediators of the PD-L1/PD-1 and IDO1-kynurenine-AhR pathways, including vitamin D as an immunomodulatory component in 78 newly diagnosed adult AML uniformly treated with intensive therapy. Lower TLC (<30 × 10/L) and blast percentage (<67%) were associated with higher CR rates (OR=3.9, p = 0.006; OR=2.9, p = 0.025). Higher baseline activated cytotoxic-T-cells (aCTLs; CD8+ PLCγ1+) predicted better OS (18-month OS 60.9% vs. 32.2%; p = 0.023). Other baseline clinical, vitamin D, and immune parameters were not associated with OS or LFS. Post-induction, kynurenine and Treg/CTL ratio increased, while tryptophan, aCTLs, and aTreg/aCTL ratio decreased. Higher post-treatment kynurenine was associated with better OS (30% vs. 64%; p = 0.017) and LFS (44% vs. 71%; p = 0.09). These findings highlight complex, plastic immune interactions in AML with potential prognostic and therapeutic implications. Micro-abstract: This study in de novo acute myeloid leukemia (AML) demonstrates that higher baseline activated cytotoxic T cells (CD8+PLCγ1+) and increased post-induction kynurenine are novel prognostic markers associated with improved survival after intensive chemotherapy. Chemotherapeutic treatment induces dynamic immune-metabolic changes, underscoring the importance of integrating immune profiling into clinical AML management.

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