Current Concepts and Advances in Graft-Versus-Host Disease Immunology

Author:

Hill Geoffrey R.12,Betts Brian C.3,Tkachev Victor456,Kean Leslie S.456,Blazar Bruce R.7

Affiliation:

1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA;

2. Division of Medical Oncology University of Washington, Seattle, Washington 98109, USA

3. Division of Hematology, Oncology, and Blood and Marrow Transplantation, Department of Medicine, University of Minnesota, Minneapolis, Minnesota 55455, USA

4. Division of Pediatric Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA;,

5. Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02215, USA

6. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA

7. Division of Blood and Marrow Transplantation, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, USA;

Abstract

Worldwide, each year over 30,000 patients undergo an allogeneic hema-topoietic stem cell transplantation with the intent to cure high-risk hematologic malignancy, immunodeficiency, metabolic disease, or a life-threatening bone marrow failure syndrome. Despite substantial advances in donor selection and conditioning regimens and greater availability of allograft sources, transplant recipients still endure the morbidity and mortality of graft-versus-host disease (GVHD). Herein, we identify key aspects of acute and chronic GVHD pathophysiology, including host/donor cell effectors, gut dysbiosis, immune system and cytokine imbalance, and the interface between inflammation and tissue fibrosis. In particular, we also summarize the translational application of this heightened understanding of immune dysregulation in the design of novel therapies to prevent and treat GVHD.

Publisher

Annual Reviews

Subject

Immunology,Immunology and Allergy

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