Distinct baseline bone marrow immune cell states were associated with early relapse in patients with newly diagnosed multiple myeloma, and tumor–immune signaling programs linked to inflammation may contribute to aggressive disease biology, according to findings from a single-cell analysis of the bone marrow immune microenvironment using the Immune Atlas of MM tool.1,2 Investigators also identified a dysfunctional T-cell population that appeared to suppress antitumor immunity rather than mount an effective immune response against myeloma cells.
The Immune Atlas of Multiple Myeloma was developed by generating profiles of 1,397,272 single cells extracted from the bone marrow of patients with newly diagnosed multiple myeloma (n = 337), which allowed for the characterization of immune and hematopoietic cell populations.1
“This Immune Atlas provides a roadmap for the next generation of myeloma care,” study coauthor Ravi Vij, MD, stated in a news release.2 “As immunotherapies like CAR [T-cell therapies] and bispecific antibodies become central to treatment, understanding the immune context in which they operate is essential. Clinically, this work lays the foundation for immune-informed risk stratification and rational development of new therapies that not only target the tumor but also restore effective anti-myeloma immunity.”
Vij is the Jeffrey S. and Prue H. Gershman Distinguished Professor of Medicine at Washington University School of Medicine in St. Louis, Missouri.
In the 1,149,344 high-quality bone marrow cells evaluated, the baseline bone marrow microenvironment (BMME) primarily consisted of T cells (30.51% CD8-positive; 23.39% CD4-positive), natural killer cells (6.82%), B cells (8.51%), myeloid cells (12.20%), erythroblasts and erythrocytes (7.87%), and plasma cells (9.17%).1
The analysis suggested that patients enriched for these adverse immune features at diagnosis were more likely to experience rapid disease recurrence after an initial line of therapy. Further, the signaling patterns observed between malignant plasma cells and immune subsets indicated inflammatory pathway activation that may support tumor growth, and the presence of an immunosuppressive, nonfunctional T-cell state provided a potential mechanistic explanation for impaired immune control.
“Cytogenetics alone demonstrated positive predictive capabilities, yet integrating information from the BMME could enhance stratification and guide optimal therapeutic selection. We observed that the prevalence of differentiated BMME immune cell populations can predict outcomes with good accuracy in our cohort regardless of cytogenetics,” explained lead study author, William C. Pilcher, PhD, and colleagues in their discussion of the results. “Importantly, combining tumor cytogenetics, and immune signatures can significantly improve the accuracy in stratifying myeloma outcomes.”
Pilcher is a graduate student in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Institute of Technology in Atlanta.
How was this analysis designed?
This study used a discovery-validation framework to define BMME features associated with outcomes in patients with newly diagnosed multiple myeloma. Bone marrow aspirates were collected from 337 patients enrolled in the observational Multiple Myeloma Research Foundation (MMRF) CoMMpass Study (NCT01454297), including a discovery cohort (n=263) and an independent validation cohort (n=74). CoMMpass was a large-scale, longitudinal study designed to evaluate disease progression and treatment response using patients’ genomic and molecular profiles, with participation across multiple sites.
Bone Marrow Immune Atlas in Multiple Myeloma
- A large bone marrow immune cell atlas in multiple myeloma paired single-cell profiling with outcome data to clarify how immune states track with disease aggressiveness.
- Baseline enrichment of specific immune-cell populations and inflammatory tumor–immune signaling patterns was associated with early relapse after initial therapy.
- Investigators identified a dysfunctional, immunosuppressive T-cell subset that may promote antitumor immunity, with implications for prognosis and immune-based treatment strategies.
For immune profiling, the research team performed single-cell RNA sequencing (scRNA-seq) on nearly 1.4 million individual plasma and immune cells from these bone marrow samples, enabling high-resolution characterization of cellular states and inference of how specific immune subsets may function, or become dysfunctional, in the context of multiple myeloma. Cell types and subtypes were annotated using canonical lineage markers, and multi-site technical variation was addressed with batch correction (Harmony) prior to downstream analyses linking immune features to cytogenetic risk and clinical outcomes.
“It is time for a better understanding of the immune system in multiple myeloma,” co-senior author Li Ding, PhD, the David English Smith Professor of Medicine at the Washington School of Medicine and a research member of Siteman Cancer Center, added in a news release.2 “In addition to targeting the cancerous plasma cells directly, we also want new and better ways to activate the immune system to attack the malignant cells. This large-scale immune cell atlas will serve as a critical resource to investigators studying multiple myeloma and working to develop better therapies.”
References
- Pilcher WC, Yao L, Gonzalez-Kozlova E, et al. Single-cell atlas characterizes dysregulation of the bone marrow immune microenvironment associated with outcomes in multiple myeloma. Nat Med. Published online January 9, 2026. doi:0.1038/s43018-025-01072-4
- Strait JE. Immune cells predict multiple myeloma survival, relapse. WashU Medicine. Published January 9, 2026. Accessed January 9, 2026. https://medicine.washu.edu/?p=133047&preview=1&_ppp=ffbe958c15
