A new immune cell atlas has been generated from the bone marrow of patients diagnosed with multiple myeloma, an incurable cancer. Published on January 9 in the journal Nature Cancer, this extensive study provides insights into how the immune system interacts with cancerous plasma cells. The findings may assist in predicting disease aggressiveness and patient relapse risk, potentially informing future treatment strategies and the development of novel immune-based therapies.
Introduction to Multiple Myeloma
Multiple myeloma is a cancer affecting plasma cells in the bone marrow, representing the second most common blood cancer. It accounts for approximately 15%-20% of new blood cancer diagnoses annually in the U.S. While current treatment options have extended patient survival, often exceeding a decade, the disease frequently recurs after periods of remission. Approximately 60% of patients survive five years post-diagnosis. This recurrence highlights the ongoing need for new therapeutic approaches.
Research Overview
The research aimed to achieve a deeper understanding of the immune system's role in multiple myeloma, with the goal of activating it to target malignant cells and developing improved therapies.
Methodology- The research team conducted single-cell RNA sequencing, a genetic analysis method, on individual plasma and immune cells.
- Approximately 1.4 million cells were analyzed, sourced from bone marrow samples of between 335 and 337 newly diagnosed multiple myeloma patients.
- The data originated from patients enrolled in the Multiple Myeloma Research Foundation’s (MMRF) CoMMpass Study, which tracks disease progression and treatment response based on patients' genomic and molecular profiles.
Investigators observed several key factors regarding the immune environment in multiple myeloma patients:
- Patients exhibiting specific immune cell types in their bone marrow at diagnosis demonstrated a higher likelihood of early relapse after an initial round of treatment.
- Signaling patterns between cancer cells and immune cells were identified, which may promote inflammation and contribute to cancer growth in aggressive forms of the disease.
- A subset of T cells was identified that appeared dysfunctional. Instead of targeting the tumor, these cells suppressed immune activity against the cancer. Some researchers described these cells as being in a state of immunosenescence, indicating they were present but not effectively functioning.
Clinical Implications and Future Directions
The findings suggest that incorporating knowledge of a patient's bone marrow immune environment could improve upon current methods for predicting aggressive disease courses and shortened survival. Existing risk assessment for multiple myeloma primarily relies on genetic features of cancer cells and clinical health aspects. Integrating an immune component into this analysis may enhance the accuracy of categorization.
The atlas is anticipated to serve as a resource for researchers developing new immune-based therapies, which would complement existing immune-system-based treatments such as CAR-T cells and bispecific antibodies. Further work is indicated to develop specific immune-based blood tests that clinicians could use to identify the aggressiveness of multiple myeloma cases more effectively and guide treatment selection.
Collaborating Institutions and Funding
The study was co-led by researchers at Washington University School of Medicine in St. Louis and the Icahn School of Medicine at Mount Sinai, in collaboration with the Multiple Myeloma Research Foundation (MMRF) and other institutions. The MMRF designed and funded this research. Additional collaborating institutions included the Georgia Institute of Technology, Emory University, Harvard Medical School, Beth Israel Deaconess Medical Center, and the Mayo Clinic.