Effects of Adoptive Transfer of Tolerogenic Dendritic Cells on Allograft Survival in Organ Transplantation Models: An Overview of Systematic Reviews

Journal of Immunology Research, Jul 2016

Objective. To dissect the efficacy of Tol-DC therapy with or without IS in multiple animal models of transplantation. Methods and Results. PubMed, Medline, Embase, and the Cochrane Library were searched for reviews published up to April 2015. Six systematic reviews and a total of 61 articles were finally included. Data were grouped by organ transplantation models and applied to meta-analysis. Our meta-analysis shows that Tol-DC therapy successfully prolonged allograft survival to varying extents in all except the islet transplantation models and with IS drugs further prolonged the survival of heart, skin, and islet allografts in mice, but not of heart allografts in rats. Compared with IS drugs alone, Tol-DC therapy with IS extended islet allograft survival in rats but failed to influence the survival of skin, small intestine, and heart allografts in rats or of heart and skin allografts in mice. Conclusion. Tol-DC therapy significantly prolonged multiple allograft survival and further prolonged survival with IS. However, standardized protocols for modification of Tol-DC should be established before its application in clinic.

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Effects of Adoptive Transfer of Tolerogenic Dendritic Cells on Allograft Survival in Organ Transplantation Models: An Overview of Systematic Reviews

Effects of Adoptive Transfer of Tolerogenic Dendritic Cells on Allograft Survival in Organ Transplantation Models: An Overview of Systematic Reviews Yanni Zhou,1 Juan Shan,1 Yingjia Guo,1 Shengfu Li,1 Dan Long,1 Youping Li,1,2 and Li Feng1 1Key Laboratory of Transplant Engineering and Immunology of The Ministry of Health, Regenerative Medical Research Centre, West China Hospital, Sichuan University, Chengdu 610041, China 2Chinese Cochrane Centre, Chinese Evidence-Based Medicine Centre, West China Hospital, Sichuan University, Chengdu 610041, China Received 18 February 2016; Revised 6 May 2016; Accepted 12 May 2016 Academic Editor: Marco Velasco Copyright © 2016 Yanni Zhou et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Objective. To dissect the efficacy of Tol-DC therapy with or without IS in multiple animal models of transplantation. Methods and Results. PubMed, Medline, Embase, and the Cochrane Library were searched for reviews published up to April 2015. Six systematic reviews and a total of 61 articles were finally included. Data were grouped by organ transplantation models and applied to meta-analysis. Our meta-analysis shows that Tol-DC therapy successfully prolonged allograft survival to varying extents in all except the islet transplantation models and with IS drugs further prolonged the survival of heart, skin, and islet allografts in mice, but not of heart allografts in rats. Compared with IS drugs alone, Tol-DC therapy with IS extended islet allograft survival in rats but failed to influence the survival of skin, small intestine, and heart allografts in rats or of heart and skin allografts in mice. Conclusion. Tol-DC therapy significantly prolonged multiple allograft survival and further prolonged survival with IS. However, standardized protocols for modification of Tol-DC should be established before its application in clinic. 1. Introduction Transplantation is one of the most effective methods of extending life for patients with end-stage organ failure. However, the immunosuppressive (IS) agents commonly used to prevent graft-versus-host disease and host-versus-graft disease compromise the recipient’s immune system and are associated with side effects such as infection and recurrence of disease, thus decreasing the patient’s quality of life. For this reason, induction of donor-specific tolerance without impairment of immune defense remains the holy grail of transplantation research. Dendritic cells (DCs), first described in 1973 [1], are the most effective antigen-presenting cells and are key regulators of a balanced immune system by virtue of their dual immunogenic and tolerogenic functions. Immunogenic DCs have been developed as positive therapeutic vaccines to elicit antitumor responses. The first DC vaccine, sipuleucel-T (PROVENGE®), was approved by the FDA in 2010 and has since been successfully used in prostate cancer treatment [2]. In contrast, tolerogenic DCs (Tol-DCs) lack essential costimulatory signals and/or express inhibitory signals and play a role in tolerance induction. Evidence indicates that Tol-DCs have great therapeutic potential in autoimmunity and allergy [3]. To date, several phase I trials assessing safety of Tol-DCs in rheumatoid arthritis and refractory Crohn’s disease patients were conducted [4, 5]. Moreover, mounting evidence shows that Tol-DCs are able to induce donor-specific T cell hyporesponsiveness and prolong allograft survival. As such, negative vaccines based on Tol-DCs have great potential to prevent transplant rejection. The safety of autologous Tol-DCs has so far been demonstrated in type I diabetes patients [6] and is currently being tested by Moreau et al. in kidney transplant recipients [7]. However, whether Tol-DCs can effectively prolong allograft survival and show superiority to other forms of IS therapy remains controversial. Here, we present the results of a meta-analysis of the efficacy of Tol-DCs in multiple animal models of transplantation. We evaluated allograft survival time after treatment with Tol-DCs alone, compared the relative superiority of single therapy with Tol-DCs or IS, and looked for evidence of synergy between Tol-DC and IS therapy in promoting allograft survival. 2. Methods2.1. Criteria for Considering Reviews for Inclusion and Exclusion We included systematic reviews that focused on the effects of Tol-DC injection on allograft survival compared with untreated groups in any kind of transplantation model. To be included, the reviews had to describe the outcome of interest. 2.2. Search Methods for Identification of Reviews Comprehensive literature searches were conducted in PubMed, Medline, Embase, and the Cochrane Library from database inception until April 2015. We identified relevant systematic reviews using the following as MeSH or text wo (...truncated)


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Yanni Zhou, Juan Shan, Yingjia Guo, Shengfu Li, Dan Long, Youping Li, Li Feng. Effects of Adoptive Transfer of Tolerogenic Dendritic Cells on Allograft Survival in Organ Transplantation Models: An Overview of Systematic Reviews, Journal of Immunology Research, 2016, 2016, DOI: 10.1155/2016/5730674