Division of Oncology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, United States.
Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, United States.
Front Immunol. 2024 Aug 7;15:1436968. doi: 10.3389/fimmu.2024.1436968. eCollection 2024.
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 or treating mice with 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.
天然不变型自然杀伤 T(iNKT)细胞是一种免疫细胞，兼具先天免疫和适应性免疫系统的特性，并发挥多种功能，对控制各种疾病至关重要。在小鼠模型和相关的人类研究中已经证明，iNKT 细胞可以预防移植物抗宿主病(GVHD)，其中供体移植物中高含量的 iNKT 细胞与异基因造血干细胞移植中 GVHD 减少相关。这表明，在异基因移植的情况下，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裂解，并且小鼠实验表明，激活 iNKT 细胞或用扩增的 iNKT 细胞治疗小鼠可以减少肿瘤负担。最近，研究的重点是测试经过基因修饰表达嵌合抗原受体(CAR)蛋白的 CAR-iNKT 细胞的抗肿瘤功效，以增强 iNKT 细胞的肿瘤杀伤能力。此外，其中一些方法现在正在临床试验中进行测试，已经显示出强烈的安全性信号，尽管在这些早期临床试验之后，疗效仍有待确定。在这里，我们回顾了与 iNKT 细胞在 GVHD 预防和抗肿瘤功效中的作用相关的领域进展。尽管 iNKT 领域正在以令人兴奋的速度发展，但仍有许多问题需要了解，包括 iNKT 细胞亚群免疫表型和功能关系、最佳体外扩增方法、理想的治疗方案、细胞因子支持的必要性以及异基因环境中 iNKT 细胞的排斥风险。
