PDF(Pubmed)
Abstract：
Allogeneic hematopoietic cell transplantation (HCT) has transformed over the past several decades through enhanced supportive care, reduced intensity conditioning (RIC), improved human leukocyte antigen (HLA) typing, and novel graft-versus-host disease (GVHD)-prevention and treatment strategies. Most notably, the implementation of post-transplantation cyclophosphamide (PTCy) has dramatically increased the safety and availability of this life-saving therapy. Given reductions in nonrelapse mortality (NRM) with these advances, the HCT community has placed even greater emphasis on developing ways to reduce relapse - the leading cause of death after HCT. When using RIC HCT, protection from relapse relies predominantly on graft-versus-leukemia (GVL) reactions. Donor lymphocyte infusion (DLI), adoptive cellular therapy, checkpoint inhibition, and post-HCT maintenance strategies represent approaches under study that aim to augment or synergize with the GVL effects of HCT. Optimizing donor selection algorithms to leverage GVL represents another active area of research. Many of these strategies seek to harness the effects of T cells, which for decades were felt to be the primary mediators of GVL and the focus of investigation in relapse reduction. However, there is growing interest in capitalizing on the ability of natural killer (NK) cells to yield potent anti-tumor effects. A potential advantage of NK cell-based approaches over T cell-mediated is the potential to reduce NRM in addition to relapse. By decreasing infection, without increasing the risk of GVHD, NK cells may mitigate NRM, while still yielding relapse reduction through identification and clearance of cancer cells. Most T cell-focused relapse-prevention strategies must weigh the benefits of relapse reduction against the increased risk of NRM from GVHD. In contrast, NK cells have the potential to reduce both, potentially tipping the scales significantly in favor of survival. Here, we will review the role of NK cells in GVL, optimization of NK cell match or mismatch, and burgeoning areas of research in NK cell therapy such as adoptive transfer and chimeric antigen receptor (CAR) NK cells.
摘要：
异基因造血细胞移植（HCT）在过去的几十年中通过增强的支持性治疗而发生了变化，降低强度调节(RIC)，改善人类白细胞抗原（HLA）分型，和新型移植物抗宿主病（GVHD）的预防和治疗策略。最值得注意的是,移植后环磷酰胺(PTCy)的实施显著提高了这种救命疗法的安全性和可用性.鉴于这些进展降低了非复发死亡率(NRM)，HCT社区更加重视开发减少复发的方法-复发是HCT后死亡的主要原因.使用RICHCT时，防止复发主要依赖于移植物抗白血病(GVL)反应.供者淋巴细胞输注（DLI），过继细胞疗法,检查点抑制，和HCT后维持策略代表了正在研究的旨在增强或协同HCT的GVL效应的方法。优化供体选择算法以利用GVL代表另一个活跃的研究领域。这些策略中的许多都试图利用T细胞的作用，几十年来，人们认为这是GVL的主要介质，也是减少复发的研究重点。然而,人们对利用自然杀伤（NK）细胞产生有效抗肿瘤作用的能力越来越感兴趣。基于NK细胞的方法优于T细胞介导的方法的潜在优势是除了复发之外还降低NRM的潜力。通过减少感染，在不增加GVHD风险的情况下，NK细胞可以减轻NRM，同时通过识别和清除癌细胞仍然可以减少复发。大多数以T细胞为重点的复发预防策略必须权衡减少复发的益处与GVHD引起的NRM风险增加。相比之下,NK细胞有可能减少两者，可能会使天平显着有利于生存。这里,我们将回顾NK细胞在GVL中的作用，优化NK细胞匹配或错配，以及NK细胞疗法的新兴研究领域，例如过继转移和嵌合抗原受体（CAR）NK细胞。
