不变自然杀伤 T (iNKT) 细胞是利用先天性和适应性免疫系统特性并发挥对控制各种疾病至关重要的多种功能的免疫细胞。 iNKT 细胞可预防移植物抗宿主病 (GVHD)，这一点已在小鼠模型和相关人体研究中得到证实，其中供体移植物中高 iNKT 细胞含量与同种异体造血干细胞移植中 GVHD 的减少相关。这表明在同种异体移植中增加 iNKT 细胞数量的方法可能会减少 GVHD。 iNKT 细胞还可以诱导肿瘤细胞的细胞溶解，小鼠实验表明，体内激活 iNKT 细胞或用离体扩增的 iNKT 细胞治疗小鼠可以减轻肿瘤负荷。最近，研究重点是测试经过基因改造的 iNKT 细胞的抗肿瘤功效，以表达嵌合抗原受体 (CAR) 蛋白 (CAR-iNKT) 细胞，以增强 iNKT 细胞的肿瘤杀伤能力。此外，其中几种方法目前正在临床试验中进行测试，并显示出强烈的安全信号，但在这些早期临床试验后仍有待确定疗效。在此，我们回顾一下 iNKT 细胞在 GVHD 预防和抗癌功效中的作用相关领域的进展。尽管 iNKT 领域正在以令人兴奋的速度取得进展，但关于 iNKT 细胞亚群免疫表型和功能关系、最佳离体扩增方法、理想的治疗方案、细胞因子支持的需求以及同种异体环境中 iNKT 细胞的排斥风险，还有很多需要学习的地方.版权所有 © 2024 奥尼尔、Mavers、Jayasinghe 和 DiPersio。

Invariant natural killer T (iNKT) cells are immune cells that harness properties of both the innate and adaptive immune system and exert multiple functions critical for the control of various diseases. Prevention of graft-versus-host disease (GVHD) by iNKT cells has been demonstrated in mouse models and in correlative human studies in which high iNKT cell content in the donor graft is associated with reduced GVHD in the setting of allogeneic hematopoietic stem cell transplants. This suggests that approaches to increase the number of iNKT cells in the setting of an allogeneic transplant may reduce GVHD. iNKT cells can also induce cytolysis of tumor cells, and murine experiments demonstrate that activating iNKT cells in vivo or treating mice with ex vivo expanded iNKT cells can reduce tumor burden. More recently, research has focused on testing anti-tumor efficacy of iNKT cells genetically modified to express a chimeric antigen receptor (CAR) protein (CAR-iNKT) cells to enhance iNKT cell tumor killing. Further, several of these approaches are now being tested in clinical trials, with strong safety signals demonstrated, though efficacy remains to be established following these early phase clinical trials. Here we review the progress in the field relating to role of iNKT cells in GVHD prevention and anti- cancer efficacy. Although the iNKT field is progressing at an exciting rate, there is much to learn regarding iNKT cell subset immunophenotype and functional relationships, optimal ex vivo expansion approaches, ideal treatment protocols, need for cytokine support, and rejection risk of iNKT cells in the allogeneic setting.Copyright © 2024 O’Neal, Mavers, Jayasinghe and DiPersio.