Delayed Transfer of Immune Cells or the Art of Donor Lymphocyte Infusion (DLI) 2.0

Author:

Falkenburg J. H. Frederik,Schmid Christoph,Kolb Hans Joachim,Kuball Jürgen

Abstract

AbstractIn the context of an allogeneic hematopoietic cell transplantation (HCT), the interplay between host and donor immune cells is considered to be the primary mechanism responsible for graft-versus-leukemia (GVL) reactivity and also able to mediate graft-versus-host disease (GVHD) (Schmid et al. 2021). The tissue specificity of the immune response determines the balance between GVL and GVHD, as well as tropism of GVHD. The main population for success and failure of HCT and DLIs originates from αβT cells. Other subsets are also key modulators of efficacy. For example, NK cells most likely provide acute control of leukemia and of infections like CMV. However, NK cells become rapidly educated over time (Orr and Lanier 2010) and lose their antileukemia activity. Thus, donor transfer of NK cells is obsolete and needs additional, for example, genetic modification to engineer long-term efficacy (Laskowski et al. 2022; Liu et al. 2020). Other subsets, like γδT cells, appear to have a more prolonged antileukemia effect (Handgretinger and Schilbach 2018; Sebestyen et al. 2020) and are also helpful in controlling CMV reactivation (Scheper et al. 2013; de Witte et al. 2018). However, also, donor γδT cells can lose activity over time, and sustainable activity requires, outside the context of an HCT, most likely further modifications (Sebestyen et al. 2020; Li et al. 2023). NKT cells, like regulatory T cells, have been mainly reported to influence GVHD. While an increase in NKT cells in the graft associates with a reduced GVHD incidence (Malard et al. 2016), depletion of regulatory T cells in donor lymphocyte infusions (DLI) improves GVL effects, although it augments the risk of GVHD (Maury et al. 2010). Thus, lymphocyte infusions as part of the graft at the time of transplantation, or delayed as DLI, have multiple effector cells that need to be considered in terms of different alloreactive effects (for review see also (Schmid et al. 2021)).

Publisher

Springer International Publishing

Reference47 articles.

1. Admiraal R, Nierkens S, de Witte MA, Petersen EJ, Fleurke GJ, Verrest L, Belitser SV, Bredius RGM, Raymakers RAP, Knibbe CAJ, Minnema MC, van Kesteren C, Kuball J, Boelens JJ. Association between anti-thymocyte globulin exposure and survival outcomes in adult unrelated haemopoietic cell transplantation: a multicentre, retrospective, pharmacodynamic cohort analysis. Lancet Haematol. 2017;4:e183–91.

2. Alyea EP, DeAngelo DJ, Moldrem J, Pagel JM, Przepiorka D, Sadelin M, Young JW, Giralt S, Bishop M, Riddell S. NCI first international workshop on the biology, prevention and treatment of relapse after allogeneic hematopoietic cell transplantation: report from the committee on prevention of relapse following allogeneic cell transplantation for hematologic malignancies. Biol Blood Marrow Transplant. 2010;16:1037–69.

3. Bleakley M, Heimfeld S, Loeb KR, Jones LA, Chaney C, Seropian S, Gooley TA, Sommermeyer F, Riddell SR, Shlomchik WD. Outcomes of acute leukemia patients transplanted with naive T cell-depleted stem cell grafts. J Clin Invest. 2015;125:2677–89.

4. Boelens JJ, Admiraal R, Kuball J, Nierkens S. Fine-tuning antithymocyte globulin dosing and harmonizing clinical trial design. J Clin Oncol. 2018;36:1175–6.

5. Bug G, Burchert A, Wagner EM, Kroger N, Berg T, Guller S, Metzelder SK, Wolf A, Hunecke S, Bader P, Schetelig J, Serve H, Ottmann OG. Phase I/II study of the deacetylase inhibitor panobinostat after allogeneic stem cell transplantation in patients with high-risk MDS or AML (PANOBEST trial). Leukemia. 2017;31:2523–5.

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3