Novel Biomarkers Help to Predict Rejection after Stem Cell Transplantation Found The latest study by Dr. Sophie Paczesny and others at MUSC Hollings Cancer Center revealed a new class of immune cell biomarkers, which may reveal which patients are most at risk of graft-versus-host disease (GVHD). This study was published on Science Translational Medicine.
Paczesny, director of the Department of Microbiology and Immunology at MUSC, explained: “Allogeneic HSCT remains the only effective therapy for leukemia. In HSCT, donor-matched cells are injected into the blood of diseased patients and eventually enter the bone marrow. Some of these cells differentiate into immune cells that help eliminate residual leukemia cancer cells that are not killed by chemotherapy. However, some donors' immune cells may attack the patient's own healthy tissue at the same time, which is called graft-versus-host disease.” GVHD affects up to 50% of patients undergoing HSCT and can manifest in multiple organs. About one-third of people with GVHD experience localized effects in the gastrointestinal tract (GI-GVHD), posing the highest risk of death. This phenomenon was further described by Paczesny. “For leukemia patients, the donor cells you provide have different biological or antigenic characteristics than the recipients. This is how these immune cells recognize leukemia and destroy leukemia. However, these antigens are also present in normal tissues especially in body regions with the most microbiota (such as the gut). Therefore, donor immune cells flare up there and symptoms are most difficult to treat.” Bone marrow stem cells are called pluripotent stem cells, which means that they can mature into many different types of cells. This includes red and white blood cells and other immune cell types responsible for balancing immunity and tolerance, such as dendritic cells and T cells. Dendritic cells are able to exchange information with T cells through antigen molecules presented by MHC complexes on the cell surface. T cells are activated in recognition of "nonself" antigens and then play a key role in triggering the body's other defense systems against foreign invaders, which may include transplanted cells from different hosts. Previous work from the Paczesny laboratory has shown that immune cell signaling pathways in GI-GVHD increase the number of "hyperactivated" pathogenic T cells (Th17 cells) in the blood of these patients. The presence of these aggressive T cells was associated with lower survival compared to patients lacking GVHD or with milder forms of GVHD in the skin. These cells are also unique in their ability to induce ICOS, a class of T cell signaling coreceptors. Paczesny said. “We are trying to understand where the activation of these T cells comes from. What antigen-presenting cells are?” Since ICOS ligands are located on the surface of antigen-presenting cells, such as dendritic cells, they can be easily detected using existing technologies, such as flow cytometry, which