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Combining Intravital Fluorescent Microscopy IVFM with Genetic Models to Study Engraftment Dynamics of Hematopoietic Cells to Bone Marrow Niches

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

Gege Gui^1,2,3, Molly A Bingham⁴, Julius R Herzog⁴

¹Fralin Biomedical Research Institute, Virginia Tech FBRI Cancer Research Center, Washington, DC.

Biorxiv : the Preprint Server for Biology

|February 20, 2025

Summary

This study reveals how immune cells interact with leukemia cells in the bone marrow after treatment with pembrolizumab and decitabine. Pembrolizumab treatment altered immune cell proximity to leukemia cells, suggesting a mechanism for improved patient responses.

Keywords:

AML immunotherapy spatial transcriptomics

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Published on: November 10, 2023

Area of Science:

Oncology
Immunology
Bioinformatics

Background:

Allogeneic hematopoietic stem cell transplant shows graft-versus-leukemia effects in refractory/relapsed acute myeloid leukemia.
Immunotherapies are explored in non-transplant settings for acute myeloid leukemia.

Purpose of the Study:

Investigate spatiotemporal interactions between leukemia and immune cells in the bone marrow niche.
Analyze the effects of combining pembrolizumab (immune checkpoint inhibitor) and decitabine (hypomethylating agent) in refractory/relapsed acute myeloid leukemia patients.

Main Methods:

Multi-omic approach integrating single-cell RNA sequencing and spatial transcriptomics.
Advanced cell segmentation models (nuclear, membrane) for accurate transcript assignment.
Deep learning-based image analysis and cell-cell distance quantification (edge-based).

Main Results:

Pembrolizumab treatment led to global or local enrichment of immune cell types proximal to leukemia cells.
These spatial changes in the tumor microenvironment may correlate with clinical responses.
Ligand-receptor analysis suggested increased TWEAK signaling between leukemia and immune cells post-pembrolizumab.

Conclusions:

Pembrolizumab influences immune cell distribution around leukemia cells in the bone marrow niche.
Altered immune cell proximity and TWEAK signaling may contribute to therapeutic efficacy in acute myeloid leukemia.