Dana-Farber Cancer Institute researchers have made a breakthrough in identifying key factors that determine the success of donor lymphocyte infusion (DLI) therapy for patients with acute myeloid leukemia (AML) who have relapsed after allogenic hematopoietic stem cell transplant. Their findings, published in Science Immunology, shed light on the role of specific cell types in the DLI product and features of the tumor microenvironment in determining treatment outcomes.
Lead author Katie Maurer, MD, Ph.D., explains, “Relapse of AML after stem cell transplant is a major challenge with few effective therapies available.” Stem cell transplants offer hope for patients with AML by replacing cancerous hematopoietic stem cells with healthy donor cells, including immune cells that can target remaining leukemia cells. However, approximately one in three patients experience relapse after transplant, prompting the need for DLI therapy.
DLI involves infusing white blood cells from the donor into the patient to boost the immune response against leukemia cells. While DLI is successful in only a minority of patients, Maurer and principal investigator Catherine Wu, MD, sought to uncover the underlying factors influencing treatment efficacy. By analyzing bone marrow samples from patients who received DLI, the researchers identified distinct cellular populations associated with treatment response.
Using single-cell sequencing techniques, the team observed that patients who responded to DLI had unique immune cell profiles compared to non-responders. This distinction suggests the presence of “hot” and “cold” forms of AML, similar to patterns seen in solid tumors. Additionally, a specific subset of CD8+ cytotoxic T lymphocytes expressing the ZNF683/Hobit transcription factor emerged as key mediators of the graft versus leukemia effect in responsive patients. These cells coordinate with other immune cells to target and eliminate leukemia cells.
Importantly, the researchers found that this critical cell type originates in the DLI product itself, highlighting the role of donor immune cells in driving therapeutic responses. Maurer emphasizes the potential of this discovery in developing more effective T cell therapies for AML treatment. By understanding the mechanisms underlying treatment response, researchers aim to improve therapeutic strategies and outcomes for a broader range of patients.
The study, titled “Coordinated immune networks in leukemia bone marrow microenvironments distinguish response to cellular therapy,” provides valuable insights into optimizing DLI therapy for AML patients. This research opens doors for the development of targeted immunotherapies with enhanced efficacy in treating relapsed leukemia cases.
For more information, the full study can be accessed in Science Immunology. This groundbreaking research was conducted by Dana-Farber Cancer Institute, underscoring the institution’s commitment to advancing cancer treatment and care.
Reference:
Katie Maurer et al, Coordinated immune networks in leukemia bone marrow microenvironments distinguish response to cellular therapy, Science Immunology (2025). DOI: 10.1126/sciimmunol.adr0782
Provided by Dana-Farber Cancer Institute. For more information, visit www.dana-farber.org.
