Single-Cell and Multi-Omics Profiling of the Multiple Myeloma Immune Niche: From Bone Marrow Architecture and Metabolic Reprogramming to Immunotherapy Response.
- 1Department of Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel.
- 2Jerusalem Multidisciplinary College, Jerusalem 9101001, Israel.
Abstract
Multiple myeloma (MM) is increasingly understood as a spatially organized and dynamically evolving disease, in which malignant plasma-cell behavior is shaped by local immune, stromal, vascular, and metabolic contexts. Single-cell, spatial, and multi-omic technologies have resolved tumor-cell heterogeneity, bone marrow niche remodeling, immune dysfunction, and therapy-induced selection at unprecedented resolution, yet an integrated synthesis linking marrow architecture, extramedullary dissemination, circulating tumor cells, metabolic reprogramming, chimeric antigen receptor T (CAR-T) cell and T-cell-redirecting immunotherapy, and stem-cell transplantation remains lacking. Here, we review how malignant subclones occupy distinct marrow regions, focal lesions, and extramedullary sites with different transcriptional, antigenic, immune-interactive, and metabolic states. We discuss how spatial transcriptomics and multiplexed imaging reveal immune exclusion, stromal support, oxidative and glycolytic niches, and region-specific antigen heterogeneity. We further examine how circulating tumor cells serve as liquid readouts of tumor burden, high-risk genomics, and clonal evolution. Emphasis is placed on CAR T-cell and T-cell engager therapies, where response and resistance depend on antigen retention, effector-cell fitness, clonal T-cell expansion, myeloid suppression, and spatial accessibility. Finally, we consider autologous hematopoietic stem-cell transplantation as a clinical model of cytoreduction, lymphodepletion, and incomplete immune reconstitution. We propose that MM progression and relapse should be interpreted through an integrated spatial-temporal framework, in which therapeutic outcome reflects the interaction between malignant plasma-cell plasticity, immune competence, stromal persistence, metabolic adaptation, and residual disease localization.
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BibTeX
@article{beider2026singlecell,
title = {{Single-Cell and Multi-Omics Profiling of the Multiple Myeloma Immune Niche: From Bone Marrow Architecture and Metabolic Reprogramming to Immunotherapy Response.}},
author = {Katia Beider and Olga Ostrovsky and Arnon Nagler},
journal = {Cancers},
year = {2026},
month = sep,
doi = {10.3390/cancers18193158},
url = {https://europepmc.org/article/MED/42882852},
note = {CC BY},
}
RIS
TY - JOUR
TI - Single-Cell and Multi-Omics Profiling of the Multiple Myeloma Immune Niche: From Bone Marrow Architecture and Metabolic Reprogramming to Immunotherapy Response.
AU - Katia Beider
AU - Olga Ostrovsky
AU - Arnon Nagler
PY - 2026
DA - 2026/09/29
JO - Cancers
DO - 10.3390/cancers18193158
UR - https://europepmc.org/article/MED/42882852
AB - Multiple myeloma (MM) is increasingly understood as a spatially organized and dynamically evolving disease, in which malignant plasma-cell behavior is shaped by local immune, stromal, vascular, and metabolic contexts. Single-cell, spatial, and multi-omic technologies have resolved tumor-cell heterogeneity, bone marrow niche remodeling, immune dysfunction, and therapy-induced selection at unprecedented resolution, yet an integrated synthesis linking marrow architecture, extramedullary dissemination, circulating tumor cells, metabolic reprogramming, chimeric antigen receptor T (CAR-T) cell and T-cell-redirecting immunotherapy, and stem-cell transplantation remains lacking. Here, we review how malignant subclones occupy distinct marrow regions, focal lesions, and extramedullary sites with different transcriptional, antigenic, immune-interactive, and metabolic states. We discuss how spatial transcriptomics and multiplexed imaging reveal immune exclusion, stromal support, oxidative and glycolytic niches, and region-specific antigen heterogeneity. We further examine how circulating tumor cells serve as liquid readouts of tumor burden, high-risk genomics, and clonal evolution. Emphasis is placed on CAR T-cell and T-cell engager therapies, where response and resistance depend on antigen retention, effector-cell fitness, clonal T-cell expansion, myeloid suppression, and spatial accessibility. Finally, we consider autologous hematopoietic stem-cell transplantation as a clinical model of cytoreduction, lymphodepletion, and incomplete immune reconstitution. We propose that MM progression and relapse should be interpreted through an integrated spatial-temporal framework, in which therapeutic outcome reflects the interaction between malignant plasma-cell plasticity, immune competence, stromal persistence, metabolic adaptation, and residual disease localization.
SN - 2072-6694
ER -