صورة الغلاف

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

محفوظ في:
الحاوية / القاعدة:bioRxiv (Jan 27, 2025)
المؤلف الرئيسي: Gui, Gege
مؤلفون آخرون: 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
منشور في:
Cold Spring Harbor Laboratory Press
الموضوعات:
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
الوصول للمادة أونلاين:Citation/Abstract
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مستخلص: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
تدمد:2692-8205
DOI:10.1101/2025.01.24.634753
المصدر:Biological Science Database