Leveque Lucie, Le Texier Laetitia, Lineburg Katie E, Hill Geoffrey R, MacDonald Kelli P A
Department of Immunology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Immunol Cell Biol. 2015 Jan;93(1):43-50. doi: 10.1038/icb.2014.95. Epub 2014 Nov 4.
Allogeneic haematopoietic stem cell transplantation (HSCT) represents the only curative therapy for the majority of bone marrow-derived cancers. Unfortunately, HSCT can result in serious complications such as graft-versus-host disease, graft failure and infection. In the last decade, there have been major advances in the understanding of the role of autophagy in many diseases and cellular processes. Recent findings have demonstrated a crucial role for autophagy in haematopoietic stem cell survival and function, antigen presentation, T-cell differentiation and response to cytokine stimulation. Given the critical requirement for each of these processes in HSCT and subsequent complications, it is surprising that the contribution of autophagy to HSCT per se is relatively unexplored. In addition, the increasing use of autophagy-modulating drugs in the clinic further highlights the need to understand the role of autophagy in allogeneic HSCT. This review will cover established and implicated roles of autophagy in HSCT, suggesting this pathway as an important therapeutic target for improving transplant outcomes.
异基因造血干细胞移植(HSCT)是大多数骨髓源性癌症的唯一治愈性疗法。不幸的是,HSCT可导致严重并发症,如移植物抗宿主病、移植物失败和感染。在过去十年中,人们对自噬在许多疾病和细胞过程中的作用的理解有了重大进展。最近的研究结果表明,自噬在造血干细胞存活和功能、抗原呈递、T细胞分化以及对细胞因子刺激的反应中起着关键作用。鉴于HSCT及后续并发症中每个过程都至关重要,令人惊讶的是,自噬对HSCT本身的贡献相对未被探索。此外,临床上自噬调节药物的使用日益增加,进一步凸显了了解自噬在异基因HSCT中作用的必要性。本综述将涵盖自噬在HSCT中已确立和涉及的作用,表明该途径是改善移植结果的重要治疗靶点。