Translational Clinical Strategies for the Prevention of Gastrointestinal Tract Graft Versus Host Disease. Front Immunol 2021;12:779076
Date
12/14/2021Pubmed ID
34899738Pubmed Central ID
PMC8662938DOI
10.3389/fimmu.2021.779076Scopus ID
2-s2.0-85121218490 (requires institutional sign-in at Scopus site) 2 CitationsAbstract
Graft versus host disease (GVHD) is the major non-relapse complication associated with allogeneic hematopoietic stem cell transplantation (HSCT). Unfortunately, GVHD occurs in roughly half of patients following this therapy and can induce severe life-threatening side effects and premature mortality. The pathophysiology of GVHD is driven by alloreactive donor T cells that induce a proinflammatory environment to cause pathological damage in the skin, gastrointestinal (GI) tract, lung, and liver during the acute phase of this disease. Recent work has demonstrated that the GI tract is a pivotal target organ and a primary driver of morbidity and mortality in patients. Prevention of this complication has therefore emerged as an important goal of prophylaxis strategies given the primacy of this tissue site in GVHD pathophysiology. In this review, we summarize foundational pre-clinical studies that have been conducted in animal models to prevent GI tract GVHD and examine the efficacy of these approaches upon subsequent translation into the clinic. Specifically, we focus on therapies designed to block inflammatory cytokine pathways, inhibit cellular trafficking of alloreactive donor T cells to the GI tract, and reconstitute impaired regulatory networks for the prevention of GVHD in the GI tract.
Author List
Rayasam A, Drobyski WRAuthor
William R. Drobyski MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Adoptive TransferAnimals
Anti-Inflammatory Agents
Chemotaxis, Leukocyte
Cytokines
Disease Models, Animal
Gastrointestinal Diseases
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Humans
Immunosuppressive Agents
Immunotherapy
Inflammation Mediators
Molecular Targeted Therapy
Signal Transduction
T-Lymphocytes
Transplantation, Homologous
