Single Cell Spatial Transcriptomics Reveals Immunotherapy-Driven Bone Marrow Niche Remodeling in AML

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Dades bibliogràfiques
Publicat a:	bioRxiv (Jan 27, 2025)
Autor principal:	Gui, Gege
Altres autors:	Bingham, Molly Anne, Julius Raimund Herzog, Wong-Rolle, Abigail, Dillon, Laura W, Goswami, Meghali, Martin, Edward, Reeves, Jason, Kim, Sean, Bahrami, Arya, Degenhardt, Hermann, Zaki, George, Prajan Divakar, Schrom, Edward C, Calvo, Katherine, Hourigan, Christopher S, Hansen, Kasper D, Chen, Zhao
Publicat:	Cold Spring Harbor Laboratory Press
Matèries:	Hematopoietic stem cells Acute myeloid leukemia Bone marrow transplantation Leukemia Immunotherapy Immune checkpoint inhibitors Pembrolizumab Segmentation Stem cell transplantation Cell culture 5-aza-2'-deoxycytidine Bone remodeling Image processing Tumor microenvironment Bone marrow Transcriptomics Patients Deep learning Allografts
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Descripció
Resum:	Given the successful graft-versus-leukemia cell treatment effect observed with allogeneic hematopoietic stem cell transplant for patients with refractory or relapsed acute myeloid leukemia, immunotherapies have also been investigated in the nontransplant setting. Here, we use a multi-omic approach to investigate spatiotemporal interactions in the bone marrow niche between leukemia cells and immune cells in patients with refractory or relapsed acute myeloid leukemia treated with a combination of the immune checkpoint inhibitor pembrolizumab and hypomethylating agent decitabine. We derived precise segmentation data by extensively training nuclear and membrane cell segmentation models, which enabled accurate transcript assignment and deep learning-feature-based image analysis. To overcome read-depth limitations, we integrated the single-cell RNA sequencing data with single-cell-resolution spatial transcriptomic data from the same sample. Quantifying cell-cell distances between cell edges rather than cell centroids allowed us to conduct a more accurate downstream analysis of the tumor microenvironment, revealing that multiple cell types of interest had global enrichment or local enrichment proximal to leukemia cells after pembrolizumab treatment, which could be associated with their clinical responses. Furthermore, ligand-receptor analysis indicated a potential increase in TWEAK signaling between leukemia cells and immune cells after pembrolizumab treatment.Competing Interest StatementJ.D., S.K., A.B., and P.D. are employees and stockholders at NanoString Technologies Inc. All other authors declare no competing interests.Footnotes* https://github.com/chenzhaolab2023/AML-Spatial
ISSN:	2692-8205
DOI:	10.1101/2025.01.24.634753
Font:	Biological Science Database