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      Advance in Targeted Immunotherapy for Graft-Versus-Host Disease

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          Abstract

          Graft-versus-host disease (GVHD) is a serious and deadly complication of patients, who undergo hematopoietic stem cell transplantation (HSCT). Despite prophylactic treatment with immunosuppressive agents, 20–80% of recipients develop acute GVHD after HSCT. And the incidence rates of chronic GVHD range from 6 to 80%. Standard therapeutic strategies are still lacking, although considerable advances have been gained in knowing of the predisposing factors, pathology, and diagnosis of GVHD. Targeting immune cells, such as regulatory T cells, as well as tolerogenic dendritic cells or mesenchymal stromal cells (MSCs) display considerable benefit in the relief of GVHD through the deletion of alloactivated T cells. Monoclonal antibodies targeting cytokines or signaling molecules have been demonstrated to be beneficial for the prevention of GVHD. However, these remain to be verified in clinical therapy. It is also important and necessary to consider adopting individualized treatment based on GVHD subtypes, pathological mechanisms involved and stages. In the future, it is hoped that the identification of novel therapeutic targets and systematic research strategies may yield novel safe and effective approaches in clinic to improve outcomes of GVHD further. In this article, we reviewed the current advances in targeted immunotherapy for the prevention of GVHD.

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          Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells.

          Adult bone-marrow-derived mesenchymal stem cells are immunosuppressive and prolong the rejection of mismatched skin grafts in animals. We transplanted haploidentical mesenchymal stem cells in a patient with severe treatment-resistant grade IV acute graft-versus-host disease of the gut and liver. Clinical response was striking. The patient is now well after 1 year. We postulate that mesenchymal stem cells have a potent immunosuppressive effect in vivo.
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            Advances in graft-versus-host disease biology and therapy.

            Allogeneic haematopoietic stem cell transplantation is used to treat a variety of disorders, but its efficacy is limited by the occurrence of graft-versus-host disease (GVHD). The past decade has brought impressive advances in our understanding of the role of stimulatory and suppressive elements of the adaptive and innate immune systems from both the donor and the host in GVHD pathogenesis. New insights from basic immunology, preclinical models and clinical studies have led to novel approaches for prevention and treatment. This Review highlights the recent advances in understanding the pathophysiology of GVHD and its treatment, with a focus on manipulations of the immune system that are amenable to clinical application.
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              First- and second-line systemic treatment of acute graft-versus-host disease: recommendations of the American Society of Blood and Marrow Transplantation.

              Despite prophylaxis with immunosuppressive agents or a variety of other approaches, many patients suffer from acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation. Although consensus has emerged supporting the use of high-dose methylprednisolone or prednisone for initial treatment of aGVHD, practices differ among centers with respect to the initial glucocorticoid dose, the use of additional immunosuppressive agents, and the approach to withdrawal of treatment after initial improvement. Despite many studies, practices vary considerably with respect to the selection of agents for treatment of glucocorticoid-resistant or refractory GVHD. Investigators and clinicians have recognized the lack of progress and lamented the absence of an accepted standard of care for secondary treatment of aGVHD. The American Society of Blood and Marrow Transplantation has developed recommendations for treatment of aGVHD to be considered by care providers, based on a comprehensive and critical review of published reports. Because the literature provides little basis for a definitive guideline, this review also provides a framework for the interpretation of previous results and the design of future studies. Copyright © 2012 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                16 May 2018
                2018
                : 9
                : 1087
                Affiliations
                [1] 1Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-Inflammatory and Immunopharmacology of Education, Ministry of China, Anti-Inflammatory Immune Drugs Collaborative Innovation Center , Hefei, Anhui, China
                [2] 2Division of Hematology, Department of Internal Medicine, College of Medicine, The Ohio State University , Columbus, OH, United States
                Author notes

                Edited by: Djordje Miljkovic, Institute for Biological Research Sinisa Stankovic, Serbia

                Reviewed by: Benedetto Bruno, Università degli Studi di Torino, Italy; Ignacio Anegon, University of Nantes, France

                *Correspondence: Lingling Zhang, ll-zhang@ 123456hotmail.com ; Wei Wei, wwei@ 123456ahmu.edu.cn

                Specialty section: This article was submitted to Alloimmunity and Transplantation, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2018.01087
                5964137
                29868032
                5f490e1e-ef49-408a-ba88-b56ff920833c
                Copyright © 2018 Zhang, Yu and Wei.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 10 February 2018
                : 01 May 2018
                Page count
                Figures: 3, Tables: 2, Equations: 0, References: 92, Pages: 12, Words: 9730
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81473223, 81330081, 81673444
                Funded by: Anhui province Postdoctoral Science Foundation
                Award ID: 2016B134
                Categories
                Immunology
                Review

                Immunology
                graft-versus-host disease,immunotherapy,immune inhibitors,immune cells,hematopoietic stem cell transplantation

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