Single-cell spatial transcriptomics reveals immunotherapy-driven bone marrow niche remodeling in AML.

Journal: Science advances
Published Date: Jul 9, 2025

Abstract

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.

Authors

  • Gege Gui
    Fralin Biomedical Research Institute, Virginia Tech FBRI Cancer Research Center, Washington, DC, USA.
  • Molly A Bingham
    Thoracic and GI Malignancies Branch, CCR, NCI, Bethesda, MD, USA.
  • Julius R Herzog
    Thoracic and GI Malignancies Branch, CCR, NCI, Bethesda, MD, USA.
  • Abigail Wong-Rolle
    Thoracic and GI Malignancies Branch, CCR, NCI, Bethesda, MD, USA.
  • Laura W Dillon
    Fralin Biomedical Research Institute, Virginia Tech FBRI Cancer Research Center, Washington, DC, USA.
  • Meghali Goswami
    Laboratory of Myeloid Malignancies, Hematology Branch, NHLBI, Bethesda, MD, USA.
  • Eddie Martin
    Department of Laboratory Medicine, NIH Clinical Center, Bethesda, MD, USA.
  • Jason Reeves
    NanoString Technologies Inc., Seattle, WA, USA.
  • Sean Kim
    NanoString Technologies Inc., Seattle, WA, USA.
  • Arya Bahrami
    NanoString Technologies Inc., Seattle, WA, USA.
  • Hermann F Degenhardt
    Protein-Nucleic Acid Interaction Section, Center for Structural Biology, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.
  • George Zaki
    Biomedical Informatics and Data Science Directorate, Frederick National Laboratory for Cancer Research (FNLCR), Frederick, Maryland, USA.
  • Prajan Divakar
    NanoString Technologies Inc., Seattle, WA, USA.
  • Edward C Schrom
    Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
  • Katherine R Calvo
    Department of Laboratory Medicine, NIH Clinical Center, Bethesda, MD, USA.
  • Christopher S Hourigan
    Fralin Biomedical Research Institute, Virginia Tech FBRI Cancer Research Center, Washington, DC, USA.
  • Kasper D Hansen
    Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA. khansen@jhsph.edu.
  • Chen Zhao
    Department of Ophthalmology, Fudan Eye & ENT Hospital, Shanghai, China.

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