Look for Drugs and Conditions

REpresentative Image

Dana-Farber Researchers Unlock Keys to Enhancing Cell Therapy for Leukemia

Researchers from the Dana-Farber Cancer Institute published a groundbreaking study in the journal Science Immunology. They found that there are important factors that affect how well donor lymphocyte infusion (DLI) therapy works for treating acute myeloid leukemia's (AML) relapse after allogeneic stem cell transplantation. This breakthrough sheds light on the cellular mechanisms behind treatment success, potentially paving the way for more effective therapies.

AML relapse post-stem cell transplantation presents a formidable challenge, with poor outcomes for most patients. Stem cell transplants replace cancerous haematopoietic stem cells with healthy donor cells. Any leukaemia that is still there is killed by the graft-versus-leukaemia (GVL) effect. However, about one-third of patients have a relapse.

DLI, a follow-up treatment, introduces donor-derived lymphocytes to bolster the immune response against leukaemia. However, the success rate of this treatment is only 15–20%, and the underlying mechanisms of its efficacy remain elusive to this day.

Led by Dr. Katie Maurer and Dr. Catherine Wu, the Dana-Farber team investigated 25 patients with relapsed AML treated with DLI.Utilising single-cell sequencing, the researchers profiled the cellular makeup of the patient's bone marrow to understand immune cell interactions and responses.

Their findings revealed a striking disparity in cellular populations between responders and non-responders. Patients who benefitted from DLI exhibited a "hottumour microenvironment, characterised by heightened immune activity. Conversely, non-responders displayed a "cold" microenvironment, a concept previously observed in solid tumours.

Finding a certain type of immune cell—CD8+ cytotoxic T lymphocytes—that have a lot of the transcription factor ZNF683/Hobit was crucial to the study. We found that these cells orchestrate anti-leukemic activity by interacting with other immune cells to expand their attacks on leukaemia cells.

In people who didn't respond, these T cells had lower levels of ZNF683/Hobit expression and higher levels of markers that stop them from working, which made them less effective. The study was important because it proved that these strong T cells came from the donor's stem cell graft and were brought back during DLI.

“Our goal is to uncover mechanisms driving successful DLI responses to develop therapies with broader efficacy,” said Dr. Maurer. By figuring out how important ZNF683/Hobit-expressing T cells are, this study paves the way for new treatments that target these immune cells to make them work better and help patients get better.

Dr. Wu emphasised the potential impact, saying, "This discovery not only enhances our understanding of immune mechanisms in AML but also opens avenues for developing targeted T-cell therapies that could benefit a larger patient population."

The Dana-Farber study marks a significant step forward in understanding and improving cell-based therapies for AML relapse. By pinpointing the immune factors that influence DLI success, researchers hope to transform the treatment landscape, offering new hope to patients battling AML.


0 Comments
Be first to post your comments

Post your comment

Related Articles

Ad 5