Gui Gege, Bingham Molly A, Herzog Julius R, Wong-Rolle Abigail, Dillon Laura W, Goswami Meghali, Martin Eddie, Reeves Jason, Kim Sean, Bahrami Arya, Degenhardt Hermann F, Zaki George, Divakar Prajan, Schrom Edward C, Calvo Katherine R, Hourigan Christopher S, Hansen Kasper D, Zhao Chen
Fralin Biomedical Research Institute, Virginia Tech FBRI Cancer Research Center, Washington, DC, USA.
Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Sci Adv. 2025 Jul 11;11(28):eadw4871. doi: 10.1126/sciadv.adw4871. Epub 2025 Jul 9.
Given the graft-versus-leukemia effect observed with allogeneic hematopoietic stem cell transplantation in refractory or relapsed acute myeloid leukemia (AML), immunotherapies have been explored in nontransplant settings. We applied a multiomic approach to examine bone marrow interactions in patients with AML treated with pembrolizumab and decitabine. Using extensively trained nuclear and membrane segmentation models, we achieved precise transcript assignment and deep learning-based image analysis. To address read-depth limitations, we integrated single-cell RNA sequencing with single-cell spatial transcriptomics from the same sample. Quantifying cell-cell distances at the edge level enabled more accurate tumor microenvironment analysis, revealing global and local immune cell enrichment near leukemia cells postpembrolizumab treatment, potentially linked to clinical response. Furthermore, ligand-receptor analysis indicated potential alterations in specific signaling pathways between leukemia and immune cells following immunotherapy treatment. These findings provide insights into immune interactions in AML and may inform therapeutic strategies.
鉴于在难治性或复发性急性髓系白血病（AML）的异基因造血干细胞移植中观察到移植物抗白血病效应，人们已在非移植环境中探索免疫疗法。我们应用了一种多组学方法来研究接受帕博利珠单抗和地西他滨治疗的AML患者的骨髓相互作用。通过使用经过广泛训练的细胞核和细胞膜分割模型，我们实现了精确的转录本分配和基于深度学习的图像分析。为了解决读取深度限制问题，我们将单细胞RNA测序与来自同一样本的单细胞空间转录组学相结合。在边缘水平量化细胞间距离能够进行更准确的肿瘤微环境分析，揭示帕博利珠单抗治疗后白血病细胞附近的全局和局部免疫细胞富集，这可能与临床反应相关。此外，配体-受体分析表明免疫治疗后白血病细胞与免疫细胞之间特定信号通路的潜在改变。这些发现为AML中的免疫相互作用提供了见解，并可能为治疗策略提供参考。
