Researchers at WashU Medicine and their collaborators have created an immune cell atlas of multiple myeloma, a cancer of the bone marrow. The new resource could improve prognosis and guide development of new immunotherapies.
A new study maps the immune cell landscape of bone marrow in patients with multiple myeloma, a rare cancer that develops in the plasma cells of the bone marrow and has no cure. This large immune cell atlas, which includes robust patient outcome data, provides unparalleled new insights into how the immune system interacts with cancerous plasma cells and can be used to determine how aggressive a patient’s multiple myeloma is likely to be. The knowledge may improve survival predictions, guide treatment decisions and help in the development of new immune-based therapies for patients with multiple myeloma.
Co-led by researchers at Washington University School of Medicine in St. Louis in collaboration with the Multiple Myeloma Research Foundation (MMRF) and other leading institutions across the country, the study was published recently in the journal Nature Cancer.
“It is time for a better understanding of the immune system in multiple myeloma,” said WashU Medicine co-senior author Li Ding PhD, the David English Smith Professor of Medicine and a research member of Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine. “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.”
While considered a rare cancer, multiple myeloma is the second most common blood cancer after leukaemia, accounting for about 15%-20% of new blood cancer diagnoses in the US. annually. Plasma cells are white blood cells in the bone marrow. When they grow out of control, they crowd out healthy blood cells. About 60% of patients are still living five years after diagnosis.
Many new treatment options have emerged for multiple myeloma in recent years that can extend survival for many patients, sometimes for more than a decade. Even so, the disease almost always returns after periods of remission, emphasizing the need for new and better options.
Several of the newest therapies for multiple myeloma are immune system-based, including CAR-T cells and what are known as bispecific antibodies. But researchers suspect there may yet be untapped opportunities for immune-based treatments for multiple myeloma, and the immune cell atlas is a new tool to harness in pursuit of such therapies.
The research team performed a rigorous and cutting-edge genetic analysis called single-cell RNA sequencing of almost 1.4 million individual plasma and immune cells in bone marrow sampled from 337 newly diagnosed multiple myeloma patients. This type of analysis can reveal how individual immune cells may function - or become dysfunctional - in the context of multiple myeloma.
The data describe patients enrolled in MMRF’s CoMMpass Study, which is the first large-scale, long-running study of patients with multiple myeloma focused on analysing disease progression and treatment response based on the genomic and molecular profiles of the patients. WashU Medicine is one of multiple sites participating in the CoMMpass Study.
The investigators found that patients with certain types of immune cells in their bone marrow at diagnosis were more likely than others to relapse quickly, meaning their cancer returned soon after a first round of treatment. The researchers identified signalling patterns between the cancer cells and immune cells that drive inflammation, which might be boosting the cancer’s growth in patients with aggressive disease.
The team also identified a type of T cell that had stopped working as expected and, rather than attacking the tumour as it should, acted to suppress immune activity against the cancer. Together, these findings could help make prognosis more accurate and aid in selecting the best therapies.
Importantly, the researchers showed that knowledge of the immune environment in a patient’s bone marrow could improve upon current methods for predicting which patients are most likely to experience an aggressive course of the disease and have shortened survival. Such predictions can help guide treatment decisions in terms of matching the intensity of the treatment with the aggressiveness of the cancer.
“More work is needed to develop specific immune-based blood tests, for example, that clinicians could order to better identify the aggressiveness of a particular case of multiple myeloma and help them select the best treatments for that patient,” Ding said. “This immune cell atlas fills a gap in knowledge that is needed to develop these types of new clinical tools.”
Pictured above is a sample of bone marrow from a patient with multiple myeloma, indicated by an overabundance of plasma cells (pink) compared with normal bone marrow (green). T cells are in red.
- Pilcher WC, Yao L, Gonzalez-Kozlova E, et al. A single-cell atlas characterizes dysregulation of the bone marrow immune microenvironment associated with outcomes in multiple myeloma. Nat Cancer. Published online January 9, 2026. doi:10.1038/s43018-025-01072-4.