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Dana-Farber Most cancers Institute researchers have recognized elements that decide whether or not donor lymphocyte infusion (DLI), a typical remedy for sufferers with acute myeloid leukemia (AML) who’ve relapsed after allogenic hematopoietic stem cell transplant, will efficiently transfer the affected person into remission. The workforce recognized {that a} key cell kind within the DLI product and options of the tumor microenvironment in sufferers each play a task.
The findings have been printed in Science Immunology.
“Relapse of AML after stem cell transplant is a major challenge,” says first creator Katie Maurer, MD, Ph.D.. “There are few effective therapies, and patient outcomes after relapse are poor.”
For sufferers with AML, a stem cell transplant holds the potential for a treatment. The purpose of the transplant is to interchange the affected person’s hematopoietic stem cells—cells that rejuvenate provides of blood and immune cells—with donor stem cells that aren’t cancerous. As well as, the donor cells additionally embrace lively immune cells that may assault leukemia cells that stay within the affected person after the transplant. This phenomenon known as the graft versus leukemia impact.
Nevertheless, roughly one in three sufferers with AML relapse after allogenic stem cell transplant. DLI is a follow-on therapy that may assist stave off or deal with relapse. It entails an infusion of white blood cells, known as lymphocytes, from the donor of the stem cell transplant into the affected person.
DLI is profitable in solely about 15-20% of sufferers with AML. Additional, precisely how the cells within the DLI product assist transfer leukemia into remission are usually not identified, making it troublesome for investigators to enhance the therapy.
Maurer and principal investigator Catherine Wu, MD, chief of Dana-Farber’s Division of Stem Cell Transplantation and Mobile Therapies, wished to study extra about what elements contribute to the success of DLI. To do that, they examined cells from the bone marrow of 25 sufferers with relapsed leukemia who had been handled with stem cell transplant and DLI. The pattern included sufferers who responded to DLI and sufferers who didn’t.
They employed single cell sequencing methods to deeply profile multitudes of cells from every affected person. This enabled the workforce to study not solely the vary of cell varieties within the bone marrow, but in addition how these cells have been interacting and driving immune responses within the affected person.
The discovered that sufferers who responded to DLI remedy had notably totally different mobile populations of their bone marrow in comparison with sufferers who didn’t reply. The discovering means that there is perhaps types of AML which might be “hot,” which means they reply to immune remedy, or “cold,” which means they don’t, much like the “hot” and “cold” paradigm seen in some strong tumors.
The workforce additionally recognized a single immune cell kind that seems to mediate the graft versus leukemia impact in sufferers that reply to DLI. The cell kind, CD8+ cytotoxic T lymphocytes that categorical a transcription issue known as ZNF683/Hobit at excessive ranges, seem to coordinate with different immune cells to develop and assault leukemia cells. In sufferers who didn’t reply, these T cells had decrease ranges of expression of ZNF683/Hobit and better ranges of markers that inhibit their exercise.
Additional, the workforce discovered that this cell kind originates within the DLI product. That’s, it’s current within the donor’s unique graft and re-infused throughout DLI.
“The goal of our research is to identify the ways in which some patients respond, in the hopes that uncovering these mechanisms can help us create improved therapies that are more effective for a greater number of patients,” says Maurer. “In this project, we identified a specific subset of activated T cells that have anti-leukemic activity. This discovery paves the way for creation of T cell therapies with improved efficacy in treating AML.”
Extra data:
Katie Maurer et al, Coordinated immune networks in leukemia bone marrow microenvironments distinguish response to mobile remedy, Science Immunology (2025). DOI: 10.1126/sciimmunol.adr0782
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Dana-Farber Most cancers Institute
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Researchers pinpoint keys to cell remedy response for leukemia (2025, January 24)
retrieved 24 January 2025
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