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

Author:

Gui, Gege [ORCID]

Bingham, Molly A [ORCID]

Herzog, Julius R [ORCID]

Wong-Rolle, Abigail [ORCID]

Dillon, Laura W [ORCID]

Goswami, Meghali [ORCID]

Martin, Eddie [ORCID]

Reeves, Jason

Kim, Sean

Bahrami, Arya

Degenhardt,Hermann [ORCID]

Zaki,George

Divakar, Prajan

Schrom, Edward C [ORCID]

Calvo, Katherine R

Hourigan, Christopher S [ORCID]

Hansen, Kasper D [ORCID]

Zhao, Chen [ORCID]
Author Address

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., Thoracic and GI Malignancies Branch, CCR, NCI, Bethesda, MD, USA., Laboratory of Myeloid Malignancies, Hematology Branch, NHLBI, Bethesda, MD, USA., Department of Laboratory Medicine, NIH Clinical Center, Bethesda, MD, USA., NanoString Technologies Inc., Seattle, WA, USA., Biomedical Informatics and Data Science Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Lymphocyte Biology Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD, USA.,

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.

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Author Address