Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018133 (graft-versus-host disease)
 18,032 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dissociation of graft-versus-leukemia (GvL). effects from graft-versus-host disease (GvHD) is the ultimate goal of allogeneic hematopoietic stem cell transplantation (alloHSCT) in the treatment of hematological malignancies. The pivotal role of donor T cells in both anti-leukemic and anti-host reactivity of allogeneic stem cell grafts has been known since the first transplants for fatal leukemia were performed over 25 years ago. Growing understanding of the T cell-mediated GvL response has revealed the importance of host-type antigen-presenting cells and the capacity of adoptively transferred donor T cells in inducing anti-leukemic responses, and has led to a re-evaluation of the relative roles of the pre-transplant conditioning regimen and the allogeneic stem cell graft. Key advances in clinical practice such as reduced-intensity stem cell transplantation and donor lymphocyte infusions are now routinely applied and allow for the induction of potent antileukemic effects, while GvHD can to some extent be controlled. Other strategies to separate T cell-mediated antileukemic effects from GvHD are antigen-specific adoptive T cell-therapy and recipient lymphocyte infusion (RLI) and these are in an experimental stage. Importantly, a role for alloreactive natural killer cells in mediating GvL without GvHD has emerged in patient studies of MHC haplotype-mismatched alloHSCT. Finally, experimental studies indicate that naturally occurring regulatory T cells may differentially affect GvHD and GvL.
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PMID:Can graft-versus-leukemia reactivity be dissociated from graft-versus-host disease? 1748 98

Interferon (IFN)-gamma is a pleiotropic cytokine with a central role in innate and adaptive immunity. As a potent pro-inflammatory and antitumor cytokine, IFN-gamma is conventionally thought to be responsible for driving cellular immune response. On the other hand, accumulating evidence suggests that IFN-gamma also has immunosuppressive activity. An important role for IFN-gamma in inhibiting graft-versus-host disease (GVHD) has been demonstrated in murine models, despite IFN-gamma being one of the key factors amplifying T cell activation during the process of acute GVHD (aGVHD), the major complication and cause of post-transplant mortality in allogeneic bone marrow transplantation (BMT). At the same time, IFN-gamma facilitates graft-versus-leukemia (GVL) activity. Dissociation of GVL effects from GVHD has been the ultimate goal of allogeneic BMT in the treatment of hematologic malignancies. This paradoxic role of IFN-gamma makes modulating its activity a promising strategy to maximize GVL while minimizing GVHD and improve clinical outcomes in BMT. In this review, the effects of IFN-gamma on GVHD and GVL are discussed with consideration of the mechanism of IFN-gamma action.
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PMID:Dichotomous role of interferon-gamma in allogeneic bone marrow transplant. 1982 93